Women's Health

SACRAMENTO, CALIF. – Californians will decide in November whether to lock the right to abortion into the state constitution.

If they vote “yes” on Proposition 1, they will also lock in a right that has gotten less attention: The right to birth control.

Should the measure succeed, California would become one of the first states – if not the first – to create explicit constitutional rights to both abortion and contraception.

The lawmakers and activists behind the constitutional amendment said they hope to score a one-two punch: Protect abortion in California after the U.S. Supreme Court ended the federal constitutional right to abortion under Roe v. Wade, and get ahead of what they see as the next front in the reproductive rights fight: Birth control.

“The United States Supreme Court said that the privacy and liberty protections in the United States Constitution did not extend to abortion,” said UCLA law professor Cary Franklin, an expert in constitutional law and reproductive rights who has testified before the California legislature in support of the amendment. “If they said ‘no’ on abortion, they’re probably going to say ‘no’ on birth control because that has a similar history.”

In June, the U.S. Supreme Court’s decision in Dobbs v. Jackson Women’s Health Organization ended the federal right to abortion and left states to regulate the service. In his concurring opinion, Justice Clarence Thomas said the court should revisit other cases that have created protections for Americans based on an implicit right to privacy in the U.S. Constitution, such as the 1965 case Griswold v. Connecticut, which established a federal right to contraception for married people, and which was later extended to unmarried people.

Some congressional Democrats are now trying to codify the right to contraception in federal law. In July, the U.S. House of Representatives passed the Right to Contraception Act, which would give patients the right to access and use contraception and providers the right to furnish it. But the bill has little chance of success in the U.S. Senate, where Republicans have already blocked it once.

Protecting access to contraception is popular with voters. A national poll from Morning Consult and Politico conducted in late July found that 75% of registered voters support a federal law that protects a right to birth control access.

California isn’t the only state where voters are considering reproductive rights in their constitutions.

On Aug. 2, Kansas voters decisively rejected a constitutional amendment that would have allowed state lawmakers to ban or dramatically restrict abortion. It failed by nearly 18 percentage points.

Kentucky voters will face a similar decision in November with a proposed constitutional amendment that would declare that the state’s constitutional right to privacy does not cover abortion.

Vermont is going in the opposite direction. Voters there will weigh a ballot measure in November that would add a right to “personal reproductive autonomy” to the state constitution, though it does not explicitly mention abortion or contraception. In Michigan, a proposed constitutional amendment that would guarantee a right to both abortion and contraception is expected to qualify for the November ballot.

In California, Proposition 1 would prevent the state from denying or interfering with “an individual’s reproductive freedom in their most intimate decisions, which includes their fundamental right to choose to have an abortion and their fundamental right to choose or refuse contraceptives.”

The proposed constitutional amendment doesn’t go into detail about what enshrining the right to contraception in the state constitution would mean.

California already has some of the strongest contraceptive-access laws in the country – and lawmakers are considering more proposals this year. For instance, state-regulated health plans must cover all Food and Drug Administration–approved contraception; pharmacists must dispense emergency contraception to anyone with a prescription, regardless of age; and pharmacists can prescribe birth control pills on the spot. State courts have also interpreted California’s constitution to include a right to privacy that covers reproductive health decisions.

The amendment, if adopted, could provide a new legal pathway for people to sue when they’re denied contraceptives, said Michele Goodwin, chancellor’s professor of law at the University of California, Irvine.

If a pharmacist refused to fill a birth control prescription or a cashier declined to ring up condoms, she said, customers could make a case that their rights had been violated.

Making the rights to abortion and contraception explicit in the state constitution – instead of relying on a right to privacy – would also protect against shifting political winds, said state Senate leader Toni Atkins (D–San Diego), who was the director of a women’s health clinic in the 1980s. Although California’s lawmakers and executive officers are solid supporters of abortion rights, she said, the composition of the legislature and courts’ interpretation of laws could change.

“I want to know for sure that that right is protected,” Ms. Atkins said at a legislative hearing in June. “We are protecting ourselves from future courts and future politicians.”

The amendment would solidify California’s role as a reproductive rights sanctuary as much of the country chips away at birth control availability, Ms. Goodwin added.

Experts said two forms of birth control that are vulnerable to restrictions in other states are intrauterine devices, or IUDs, and emergency contraception such as Plan B. These methods are often incorrectly conflated with abortion pills, which end a pregnancy instead of preventing it.

Nine states have laws that restrict emergency contraception – for example, by allowing pharmacies to refuse to dispense it or excluding it from state family planning programs – according to the Guttmacher Institute, a research organization that supports abortion rights. In Alabama and Louisiana this year, abortion opponents introduced legislation that would restrict or ban abortion, and would also apply to emergency contraception.

“We’re seeing an erosion of abortion access that is playing out in statehouses across the country that have and will continue to target contraceptive care as well,” said Audrey Sandusky, senior director of policy and communications for the National Family Planning and Reproductive Health Association.

Susan Arnall, vice president of California’s Right to Life League, said the proposed amendment is symbolic and merely echoes current laws. Ms. Arnall said the campaign is mostly about Democratic politicians trying to score political points.

“It just allows the pro-abort legislators to trumpet and give them talking points about how they’re doing something about the overturn of Roe v. Wade,” she said. “It is political virtue signaling. I don’t think it does much of anything else.”

Ms. Goodwin argues that the measure’s symbolism is significant and overdue. She pointed to the Civil War era, when enslaved people in Southern states could look to free states for spiritual hope and material help. “Symbolically, what that meant is a kind of beacon of hope, that those places did exist, where one’s humanity could be regarded,” Ms. Goodwin said.

But California’s reputation as a haven for contraceptive availability may not be fully warranted, said Dima Qato, PharmD, PhD, an associate professor at the University of Southern California School of Pharmacy. In her 2020 study of contraceptive access in Los Angeles County, which has some of the highest rates of teen and unintended pregnancy in the country, Dr. Qato found that only 10% of pharmacies surveyed offered pharmacist-prescribed birth control. Pharmacies in low-income and minority communities were the least likely to offer the service, Dr. Qato said, worsening disparities instead of solving them.

Dr. Qato supports the constitutional amendment but said California should focus on improving and enforcing the laws it already has.

“We don’t need more laws when we don’t address the root cause of a lack of effectiveness of these laws in these communities,” she said. “Lack of enforcement and accountability disproportionately impacts communities of color.”

This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. Rachel Bluth is a correspondent for California Healthline. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

SACRAMENTO, CALIF. – Californians will decide in November whether to lock the right to abortion into the state constitution.

If they vote “yes” on Proposition 1, they will also lock in a right that has gotten less attention: The right to birth control.

Should the measure succeed, California would become one of the first states – if not the first – to create explicit constitutional rights to both abortion and contraception.

The lawmakers and activists behind the constitutional amendment said they hope to score a one-two punch: Protect abortion in California after the U.S. Supreme Court ended the federal constitutional right to abortion under Roe v. Wade, and get ahead of what they see as the next front in the reproductive rights fight: Birth control.

“The United States Supreme Court said that the privacy and liberty protections in the United States Constitution did not extend to abortion,” said UCLA law professor Cary Franklin, an expert in constitutional law and reproductive rights who has testified before the California legislature in support of the amendment. “If they said ‘no’ on abortion, they’re probably going to say ‘no’ on birth control because that has a similar history.”

In June, the U.S. Supreme Court’s decision in Dobbs v. Jackson Women’s Health Organization ended the federal right to abortion and left states to regulate the service. In his concurring opinion, Justice Clarence Thomas said the court should revisit other cases that have created protections for Americans based on an implicit right to privacy in the U.S. Constitution, such as the 1965 case Griswold v. Connecticut, which established a federal right to contraception for married people, and which was later extended to unmarried people.

Some congressional Democrats are now trying to codify the right to contraception in federal law. In July, the U.S. House of Representatives passed the Right to Contraception Act, which would give patients the right to access and use contraception and providers the right to furnish it. But the bill has little chance of success in the U.S. Senate, where Republicans have already blocked it once.

Protecting access to contraception is popular with voters. A national poll from Morning Consult and Politico conducted in late July found that 75% of registered voters support a federal law that protects a right to birth control access.

California isn’t the only state where voters are considering reproductive rights in their constitutions.

On Aug. 2, Kansas voters decisively rejected a constitutional amendment that would have allowed state lawmakers to ban or dramatically restrict abortion. It failed by nearly 18 percentage points.

Kentucky voters will face a similar decision in November with a proposed constitutional amendment that would declare that the state’s constitutional right to privacy does not cover abortion.

Vermont is going in the opposite direction. Voters there will weigh a ballot measure in November that would add a right to “personal reproductive autonomy” to the state constitution, though it does not explicitly mention abortion or contraception. In Michigan, a proposed constitutional amendment that would guarantee a right to both abortion and contraception is expected to qualify for the November ballot.

In California, Proposition 1 would prevent the state from denying or interfering with “an individual’s reproductive freedom in their most intimate decisions, which includes their fundamental right to choose to have an abortion and their fundamental right to choose or refuse contraceptives.”

The proposed constitutional amendment doesn’t go into detail about what enshrining the right to contraception in the state constitution would mean.

California already has some of the strongest contraceptive-access laws in the country – and lawmakers are considering more proposals this year. For instance, state-regulated health plans must cover all Food and Drug Administration–approved contraception; pharmacists must dispense emergency contraception to anyone with a prescription, regardless of age; and pharmacists can prescribe birth control pills on the spot. State courts have also interpreted California’s constitution to include a right to privacy that covers reproductive health decisions.

The amendment, if adopted, could provide a new legal pathway for people to sue when they’re denied contraceptives, said Michele Goodwin, chancellor’s professor of law at the University of California, Irvine.

If a pharmacist refused to fill a birth control prescription or a cashier declined to ring up condoms, she said, customers could make a case that their rights had been violated.

Making the rights to abortion and contraception explicit in the state constitution – instead of relying on a right to privacy – would also protect against shifting political winds, said state Senate leader Toni Atkins (D–San Diego), who was the director of a women’s health clinic in the 1980s. Although California’s lawmakers and executive officers are solid supporters of abortion rights, she said, the composition of the legislature and courts’ interpretation of laws could change.

“I want to know for sure that that right is protected,” Ms. Atkins said at a legislative hearing in June. “We are protecting ourselves from future courts and future politicians.”

The amendment would solidify California’s role as a reproductive rights sanctuary as much of the country chips away at birth control availability, Ms. Goodwin added.

Experts said two forms of birth control that are vulnerable to restrictions in other states are intrauterine devices, or IUDs, and emergency contraception such as Plan B. These methods are often incorrectly conflated with abortion pills, which end a pregnancy instead of preventing it.

Nine states have laws that restrict emergency contraception – for example, by allowing pharmacies to refuse to dispense it or excluding it from state family planning programs – according to the Guttmacher Institute, a research organization that supports abortion rights. In Alabama and Louisiana this year, abortion opponents introduced legislation that would restrict or ban abortion, and would also apply to emergency contraception.

“We’re seeing an erosion of abortion access that is playing out in statehouses across the country that have and will continue to target contraceptive care as well,” said Audrey Sandusky, senior director of policy and communications for the National Family Planning and Reproductive Health Association.

Susan Arnall, vice president of California’s Right to Life League, said the proposed amendment is symbolic and merely echoes current laws. Ms. Arnall said the campaign is mostly about Democratic politicians trying to score political points.

“It just allows the pro-abort legislators to trumpet and give them talking points about how they’re doing something about the overturn of Roe v. Wade,” she said. “It is political virtue signaling. I don’t think it does much of anything else.”

Ms. Goodwin argues that the measure’s symbolism is significant and overdue. She pointed to the Civil War era, when enslaved people in Southern states could look to free states for spiritual hope and material help. “Symbolically, what that meant is a kind of beacon of hope, that those places did exist, where one’s humanity could be regarded,” Ms. Goodwin said.

But California’s reputation as a haven for contraceptive availability may not be fully warranted, said Dima Qato, PharmD, PhD, an associate professor at the University of Southern California School of Pharmacy. In her 2020 study of contraceptive access in Los Angeles County, which has some of the highest rates of teen and unintended pregnancy in the country, Dr. Qato found that only 10% of pharmacies surveyed offered pharmacist-prescribed birth control. Pharmacies in low-income and minority communities were the least likely to offer the service, Dr. Qato said, worsening disparities instead of solving them.

Dr. Qato supports the constitutional amendment but said California should focus on improving and enforcing the laws it already has.

“We don’t need more laws when we don’t address the root cause of a lack of effectiveness of these laws in these communities,” she said. “Lack of enforcement and accountability disproportionately impacts communities of color.”

This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. Rachel Bluth is a correspondent for California Healthline. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

SACRAMENTO, CALIF. – Californians will decide in November whether to lock the right to abortion into the state constitution.

If they vote “yes” on Proposition 1, they will also lock in a right that has gotten less attention: The right to birth control.

Should the measure succeed, California would become one of the first states – if not the first – to create explicit constitutional rights to both abortion and contraception.

The lawmakers and activists behind the constitutional amendment said they hope to score a one-two punch: Protect abortion in California after the U.S. Supreme Court ended the federal constitutional right to abortion under Roe v. Wade, and get ahead of what they see as the next front in the reproductive rights fight: Birth control.

“The United States Supreme Court said that the privacy and liberty protections in the United States Constitution did not extend to abortion,” said UCLA law professor Cary Franklin, an expert in constitutional law and reproductive rights who has testified before the California legislature in support of the amendment. “If they said ‘no’ on abortion, they’re probably going to say ‘no’ on birth control because that has a similar history.”

In June, the U.S. Supreme Court’s decision in Dobbs v. Jackson Women’s Health Organization ended the federal right to abortion and left states to regulate the service. In his concurring opinion, Justice Clarence Thomas said the court should revisit other cases that have created protections for Americans based on an implicit right to privacy in the U.S. Constitution, such as the 1965 case Griswold v. Connecticut, which established a federal right to contraception for married people, and which was later extended to unmarried people.

Some congressional Democrats are now trying to codify the right to contraception in federal law. In July, the U.S. House of Representatives passed the Right to Contraception Act, which would give patients the right to access and use contraception and providers the right to furnish it. But the bill has little chance of success in the U.S. Senate, where Republicans have already blocked it once.

Protecting access to contraception is popular with voters. A national poll from Morning Consult and Politico conducted in late July found that 75% of registered voters support a federal law that protects a right to birth control access.

California isn’t the only state where voters are considering reproductive rights in their constitutions.

On Aug. 2, Kansas voters decisively rejected a constitutional amendment that would have allowed state lawmakers to ban or dramatically restrict abortion. It failed by nearly 18 percentage points.

Kentucky voters will face a similar decision in November with a proposed constitutional amendment that would declare that the state’s constitutional right to privacy does not cover abortion.

Vermont is going in the opposite direction. Voters there will weigh a ballot measure in November that would add a right to “personal reproductive autonomy” to the state constitution, though it does not explicitly mention abortion or contraception. In Michigan, a proposed constitutional amendment that would guarantee a right to both abortion and contraception is expected to qualify for the November ballot.

In California, Proposition 1 would prevent the state from denying or interfering with “an individual’s reproductive freedom in their most intimate decisions, which includes their fundamental right to choose to have an abortion and their fundamental right to choose or refuse contraceptives.”

The proposed constitutional amendment doesn’t go into detail about what enshrining the right to contraception in the state constitution would mean.

California already has some of the strongest contraceptive-access laws in the country – and lawmakers are considering more proposals this year. For instance, state-regulated health plans must cover all Food and Drug Administration–approved contraception; pharmacists must dispense emergency contraception to anyone with a prescription, regardless of age; and pharmacists can prescribe birth control pills on the spot. State courts have also interpreted California’s constitution to include a right to privacy that covers reproductive health decisions.

The amendment, if adopted, could provide a new legal pathway for people to sue when they’re denied contraceptives, said Michele Goodwin, chancellor’s professor of law at the University of California, Irvine.

If a pharmacist refused to fill a birth control prescription or a cashier declined to ring up condoms, she said, customers could make a case that their rights had been violated.

Making the rights to abortion and contraception explicit in the state constitution – instead of relying on a right to privacy – would also protect against shifting political winds, said state Senate leader Toni Atkins (D–San Diego), who was the director of a women’s health clinic in the 1980s. Although California’s lawmakers and executive officers are solid supporters of abortion rights, she said, the composition of the legislature and courts’ interpretation of laws could change.

“I want to know for sure that that right is protected,” Ms. Atkins said at a legislative hearing in June. “We are protecting ourselves from future courts and future politicians.”

The amendment would solidify California’s role as a reproductive rights sanctuary as much of the country chips away at birth control availability, Ms. Goodwin added.

Experts said two forms of birth control that are vulnerable to restrictions in other states are intrauterine devices, or IUDs, and emergency contraception such as Plan B. These methods are often incorrectly conflated with abortion pills, which end a pregnancy instead of preventing it.

Nine states have laws that restrict emergency contraception – for example, by allowing pharmacies to refuse to dispense it or excluding it from state family planning programs – according to the Guttmacher Institute, a research organization that supports abortion rights. In Alabama and Louisiana this year, abortion opponents introduced legislation that would restrict or ban abortion, and would also apply to emergency contraception.

“We’re seeing an erosion of abortion access that is playing out in statehouses across the country that have and will continue to target contraceptive care as well,” said Audrey Sandusky, senior director of policy and communications for the National Family Planning and Reproductive Health Association.

Susan Arnall, vice president of California’s Right to Life League, said the proposed amendment is symbolic and merely echoes current laws. Ms. Arnall said the campaign is mostly about Democratic politicians trying to score political points.

“It just allows the pro-abort legislators to trumpet and give them talking points about how they’re doing something about the overturn of Roe v. Wade,” she said. “It is political virtue signaling. I don’t think it does much of anything else.”

Ms. Goodwin argues that the measure’s symbolism is significant and overdue. She pointed to the Civil War era, when enslaved people in Southern states could look to free states for spiritual hope and material help. “Symbolically, what that meant is a kind of beacon of hope, that those places did exist, where one’s humanity could be regarded,” Ms. Goodwin said.

But California’s reputation as a haven for contraceptive availability may not be fully warranted, said Dima Qato, PharmD, PhD, an associate professor at the University of Southern California School of Pharmacy. In her 2020 study of contraceptive access in Los Angeles County, which has some of the highest rates of teen and unintended pregnancy in the country, Dr. Qato found that only 10% of pharmacies surveyed offered pharmacist-prescribed birth control. Pharmacies in low-income and minority communities were the least likely to offer the service, Dr. Qato said, worsening disparities instead of solving them.

Dr. Qato supports the constitutional amendment but said California should focus on improving and enforcing the laws it already has.

“We don’t need more laws when we don’t address the root cause of a lack of effectiveness of these laws in these communities,” she said. “Lack of enforcement and accountability disproportionately impacts communities of color.”

This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. Rachel Bluth is a correspondent for California Healthline. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

A new study from the Centers for Disease Control and Prevention found that a surprising proportion of cases of carbapenem-resistant Enterobacterales (CRE) are found in isolates from patients in the community (CA-CRE). They had previously been thought to be health care–associated infections (HCA-CRE).

Traditionally, CRE has been thought of as a nosocomial infection, acquired in a hospital or other health care facility (nursing home, long-term acute care hospital, dialysis center, etc.). This is the first population-level study to show otherwise, with fully 10% of the CRE isolates found to be community acquired.

CREs are a group of multidrug-resistant bacteria considered an urgent health threat by the CDC because they can rapidly spread between patients, especially those who are most seriously ill and vulnerable, and because they are so difficult to treat. These patients often require treatment with toxic antibiotics, such as colistin, and carry a high mortality rate – up to 50% in some studies.

Overall, 30% of CREs carry a carbapenemase – an enzyme that can make them resistant to carbapenem antibiotics. The genes for this are readily transferable between bacteria and help account for their spread in hospitals.

But in this study, published in the American Journal of Infection Control, of the 12 isolates that underwent whole-genome sequencing, 42% of the CA-CRE isolates carried the carbapenemase gene. Lead author Sandra Bulens, MPH, a health scientist in the CDC’s division of health care quality promotion, said in an interview, “The findings highlight the potential for CP-CRE to move from health care settings into the community. The fact that 5 of the 12 isolates harbored a carbapenemase gene introduces new challenges for controlling spread of CP-CRE.”

CDC researchers analyzed data from eight U.S. metropolitan areas between 2012 and 2015 as part of the CDC’s Emerging Infections Program (EIP) health care–associated infections – community interface activity, which conducts surveillance for CRE and other drug-resistant gram-negative bacteria. Cases of CA-CRE were compared with HCA-CRE, with 1499 cases in 1,194 case-patients being analyzed. Though Klebsiella pneumoniae was the most common isolate, there were some differences between metropolitan areas.

The incidence of CRE cases per 100,000 population was 2.96 (95% confidence interval, 2.81-3.11) overall and 0.29 (95% CI, 0.25-0.25) for CA-CRE. Most CA-CRE cases were in White persons (73%) and women (84%). Urine cultures were the source of 98% of all CA-CRE cases, compared with 86% of HCA-CRE cases (P < .001). Though small numbers, the numbers of patients with CA-CRE without apparent underlying medical condition (n = 51; 37%) was greater when compared with patients with HCA-CRE (n = 36; 3%; P < .001).

Asked for independent comment, Lance Price, PhD, of George Washington University and the founding director of GW’s Antibiotic Resistance Action Center, Washington, said, “what’s striking about these data is that: ‘Who is the front line, at least in the United States for CRE?’ It’s women, older women. ... At some point, we have to frame drug resistance as a women’s health issue.”

Dr. Price noted that the 10% of patients with CA-CRE acquired it in the community. “I would argue that probably none of them had any idea, because there’s this silent community epidemic,” he said. “It’s asymptomatic carriage and transmission in the community. Somebody can be this walking reservoir of these really dangerous bacteria and have no idea.”

This is an increasingly serious problem for women, Dr. Price said, because, “with a community-acquired bladder infection, you’re going to call your doctor or go to an urgent care, and they’re not going to test you. They’re going to guess what you have, and they’re going to prescribe an antibiotic, and that antibiotic is going to fail. So then your bladder infection continues, and then you wait a few more days, and you start to get flank pain and kidney infection. ... If you start getting a fever, they might admit you. They are going to start treating you immediately, and they might miss it because you’ve got this organism that’s resistant to all the best antibiotics. ... The gateway to the blood is the UTI.”

Because of such empiric treatment and increasing resistance, the risk for treatment failure is quite high, especially for older women. Ms. Bulens, however, said that, “[although] 10% of CRE were in persons without health care risk factors, the proportion of all UTIs in this population that are CRE is going to be very, very small.”

This study involved cultures from 2012 to 2015. Before the pandemic, from 2012 to 2017, U.S. deaths from antibiotic resistance fell by 18% overall and by 30% in hospitals.

But in the first year of the COVID-19 pandemic, there was a 15% increase in infections and deaths from antibiotic-resistant (AMR), hospital-acquired bacteria. In 2020, 29,400 patients died from AMR infections. There was a 78% increase in carbapenem-resistant Acinetobacter baumannii health care–associated infections, a 35% increase in carbapenem-resistant Enterobacterales, and 32% increases in both multidrug-resistant Pseudomonas aeruginosa and extended-spectrum beta-lactamase–producing Enterobacterales. Aside from gram-negative bacteria, methicillin-resistant Staphylococcus aureus rose 13%, and Candida auris rose 60%. But owing to limited surveillance, recent sound figures are lacking.

Ms. Bulens and Dr. Price reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study from the Centers for Disease Control and Prevention found that a surprising proportion of cases of carbapenem-resistant Enterobacterales (CRE) are found in isolates from patients in the community (CA-CRE). They had previously been thought to be health care–associated infections (HCA-CRE).

Traditionally, CRE has been thought of as a nosocomial infection, acquired in a hospital or other health care facility (nursing home, long-term acute care hospital, dialysis center, etc.). This is the first population-level study to show otherwise, with fully 10% of the CRE isolates found to be community acquired.

CREs are a group of multidrug-resistant bacteria considered an urgent health threat by the CDC because they can rapidly spread between patients, especially those who are most seriously ill and vulnerable, and because they are so difficult to treat. These patients often require treatment with toxic antibiotics, such as colistin, and carry a high mortality rate – up to 50% in some studies.

Overall, 30% of CREs carry a carbapenemase – an enzyme that can make them resistant to carbapenem antibiotics. The genes for this are readily transferable between bacteria and help account for their spread in hospitals.

But in this study, published in the American Journal of Infection Control, of the 12 isolates that underwent whole-genome sequencing, 42% of the CA-CRE isolates carried the carbapenemase gene. Lead author Sandra Bulens, MPH, a health scientist in the CDC’s division of health care quality promotion, said in an interview, “The findings highlight the potential for CP-CRE to move from health care settings into the community. The fact that 5 of the 12 isolates harbored a carbapenemase gene introduces new challenges for controlling spread of CP-CRE.”

CDC researchers analyzed data from eight U.S. metropolitan areas between 2012 and 2015 as part of the CDC’s Emerging Infections Program (EIP) health care–associated infections – community interface activity, which conducts surveillance for CRE and other drug-resistant gram-negative bacteria. Cases of CA-CRE were compared with HCA-CRE, with 1499 cases in 1,194 case-patients being analyzed. Though Klebsiella pneumoniae was the most common isolate, there were some differences between metropolitan areas.

The incidence of CRE cases per 100,000 population was 2.96 (95% confidence interval, 2.81-3.11) overall and 0.29 (95% CI, 0.25-0.25) for CA-CRE. Most CA-CRE cases were in White persons (73%) and women (84%). Urine cultures were the source of 98% of all CA-CRE cases, compared with 86% of HCA-CRE cases (P < .001). Though small numbers, the numbers of patients with CA-CRE without apparent underlying medical condition (n = 51; 37%) was greater when compared with patients with HCA-CRE (n = 36; 3%; P < .001).

Asked for independent comment, Lance Price, PhD, of George Washington University and the founding director of GW’s Antibiotic Resistance Action Center, Washington, said, “what’s striking about these data is that: ‘Who is the front line, at least in the United States for CRE?’ It’s women, older women. ... At some point, we have to frame drug resistance as a women’s health issue.”

Dr. Price noted that the 10% of patients with CA-CRE acquired it in the community. “I would argue that probably none of them had any idea, because there’s this silent community epidemic,” he said. “It’s asymptomatic carriage and transmission in the community. Somebody can be this walking reservoir of these really dangerous bacteria and have no idea.”

This is an increasingly serious problem for women, Dr. Price said, because, “with a community-acquired bladder infection, you’re going to call your doctor or go to an urgent care, and they’re not going to test you. They’re going to guess what you have, and they’re going to prescribe an antibiotic, and that antibiotic is going to fail. So then your bladder infection continues, and then you wait a few more days, and you start to get flank pain and kidney infection. ... If you start getting a fever, they might admit you. They are going to start treating you immediately, and they might miss it because you’ve got this organism that’s resistant to all the best antibiotics. ... The gateway to the blood is the UTI.”

Because of such empiric treatment and increasing resistance, the risk for treatment failure is quite high, especially for older women. Ms. Bulens, however, said that, “[although] 10% of CRE were in persons without health care risk factors, the proportion of all UTIs in this population that are CRE is going to be very, very small.”

This study involved cultures from 2012 to 2015. Before the pandemic, from 2012 to 2017, U.S. deaths from antibiotic resistance fell by 18% overall and by 30% in hospitals.

But in the first year of the COVID-19 pandemic, there was a 15% increase in infections and deaths from antibiotic-resistant (AMR), hospital-acquired bacteria. In 2020, 29,400 patients died from AMR infections. There was a 78% increase in carbapenem-resistant Acinetobacter baumannii health care–associated infections, a 35% increase in carbapenem-resistant Enterobacterales, and 32% increases in both multidrug-resistant Pseudomonas aeruginosa and extended-spectrum beta-lactamase–producing Enterobacterales. Aside from gram-negative bacteria, methicillin-resistant Staphylococcus aureus rose 13%, and Candida auris rose 60%. But owing to limited surveillance, recent sound figures are lacking.

Ms. Bulens and Dr. Price reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study from the Centers for Disease Control and Prevention found that a surprising proportion of cases of carbapenem-resistant Enterobacterales (CRE) are found in isolates from patients in the community (CA-CRE). They had previously been thought to be health care–associated infections (HCA-CRE).

Traditionally, CRE has been thought of as a nosocomial infection, acquired in a hospital or other health care facility (nursing home, long-term acute care hospital, dialysis center, etc.). This is the first population-level study to show otherwise, with fully 10% of the CRE isolates found to be community acquired.

CREs are a group of multidrug-resistant bacteria considered an urgent health threat by the CDC because they can rapidly spread between patients, especially those who are most seriously ill and vulnerable, and because they are so difficult to treat. These patients often require treatment with toxic antibiotics, such as colistin, and carry a high mortality rate – up to 50% in some studies.

Overall, 30% of CREs carry a carbapenemase – an enzyme that can make them resistant to carbapenem antibiotics. The genes for this are readily transferable between bacteria and help account for their spread in hospitals.

But in this study, published in the American Journal of Infection Control, of the 12 isolates that underwent whole-genome sequencing, 42% of the CA-CRE isolates carried the carbapenemase gene. Lead author Sandra Bulens, MPH, a health scientist in the CDC’s division of health care quality promotion, said in an interview, “The findings highlight the potential for CP-CRE to move from health care settings into the community. The fact that 5 of the 12 isolates harbored a carbapenemase gene introduces new challenges for controlling spread of CP-CRE.”

CDC researchers analyzed data from eight U.S. metropolitan areas between 2012 and 2015 as part of the CDC’s Emerging Infections Program (EIP) health care–associated infections – community interface activity, which conducts surveillance for CRE and other drug-resistant gram-negative bacteria. Cases of CA-CRE were compared with HCA-CRE, with 1499 cases in 1,194 case-patients being analyzed. Though Klebsiella pneumoniae was the most common isolate, there were some differences between metropolitan areas.

The incidence of CRE cases per 100,000 population was 2.96 (95% confidence interval, 2.81-3.11) overall and 0.29 (95% CI, 0.25-0.25) for CA-CRE. Most CA-CRE cases were in White persons (73%) and women (84%). Urine cultures were the source of 98% of all CA-CRE cases, compared with 86% of HCA-CRE cases (P < .001). Though small numbers, the numbers of patients with CA-CRE without apparent underlying medical condition (n = 51; 37%) was greater when compared with patients with HCA-CRE (n = 36; 3%; P < .001).

Asked for independent comment, Lance Price, PhD, of George Washington University and the founding director of GW’s Antibiotic Resistance Action Center, Washington, said, “what’s striking about these data is that: ‘Who is the front line, at least in the United States for CRE?’ It’s women, older women. ... At some point, we have to frame drug resistance as a women’s health issue.”

Dr. Price noted that the 10% of patients with CA-CRE acquired it in the community. “I would argue that probably none of them had any idea, because there’s this silent community epidemic,” he said. “It’s asymptomatic carriage and transmission in the community. Somebody can be this walking reservoir of these really dangerous bacteria and have no idea.”

This is an increasingly serious problem for women, Dr. Price said, because, “with a community-acquired bladder infection, you’re going to call your doctor or go to an urgent care, and they’re not going to test you. They’re going to guess what you have, and they’re going to prescribe an antibiotic, and that antibiotic is going to fail. So then your bladder infection continues, and then you wait a few more days, and you start to get flank pain and kidney infection. ... If you start getting a fever, they might admit you. They are going to start treating you immediately, and they might miss it because you’ve got this organism that’s resistant to all the best antibiotics. ... The gateway to the blood is the UTI.”

Because of such empiric treatment and increasing resistance, the risk for treatment failure is quite high, especially for older women. Ms. Bulens, however, said that, “[although] 10% of CRE were in persons without health care risk factors, the proportion of all UTIs in this population that are CRE is going to be very, very small.”

This study involved cultures from 2012 to 2015. Before the pandemic, from 2012 to 2017, U.S. deaths from antibiotic resistance fell by 18% overall and by 30% in hospitals.

But in the first year of the COVID-19 pandemic, there was a 15% increase in infections and deaths from antibiotic-resistant (AMR), hospital-acquired bacteria. In 2020, 29,400 patients died from AMR infections. There was a 78% increase in carbapenem-resistant Acinetobacter baumannii health care–associated infections, a 35% increase in carbapenem-resistant Enterobacterales, and 32% increases in both multidrug-resistant Pseudomonas aeruginosa and extended-spectrum beta-lactamase–producing Enterobacterales. Aside from gram-negative bacteria, methicillin-resistant Staphylococcus aureus rose 13%, and Candida auris rose 60%. But owing to limited surveillance, recent sound figures are lacking.

Ms. Bulens and Dr. Price reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Human papillomavirus (HPV) vaccine given around the time women have surgery for precancerous cervical lesions might lead to a reduction in the risk of lesions returning, as well as other HPV-related diseases, but the effects of this remain unclear.

The authors of the new study, published in The BMJ, explained that women who have been treated for high-grade cervical intra-epithelial neoplasia (CIN) have a “lifelong residual high risk of cervical cancer and other malignancies related to HPV infection,” and some research suggests that giving a preventive HPV vaccine alongside treatment for CIN might help to “reduce the risk in these women.”

HPV vaccination is highly effective at preventing the development of precancerous cervical lesions, CIN, and in the U.K., HPV vaccination is offered to girls and boys around the age of 12 or 13.

Eluned Hughes, head of information and engagement at Jo’s Cervical Cancer Trust, said: “Recent evidence has found that cases of cervical cancer have fallen 87% since the introduction of the HPV vaccine program in U.K. schools in 2008.”

“However, women over the age of 27, for whom the vaccine was not available, remain at increased risk of cervical cancer,” she highlighted.
 

Significant risk of bias and scarcity of data

In the study, researchers set out to explore the efficacy of HPV vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing local surgical treatment of preinvasive genital disease.

The systematic review and meta-analysis, led by researchers at Imperial College London, screened data from PubMed (Medline), Scopus, Cochrane, Web of Science, and ClinicalTrials.gov from inception to March 31, 2021.

The researchers analyzed the results of 18 studies – two randomized controlled trials (RCTs), 12 observational studies, and four post-hoc analyses of RCTs.

The authors said that the two RCTs were classified as low risk of bias, while in the observational studies and post-hoc analyses, risk of bias was moderate for seven, serious for seven, and critical for two. Average length of follow-up was 36 months.

There was a reduction of 57% in the risk of recurrence of high-grade pre-invasive disease (CIN2+) in individuals who were vaccinated, compared with those who were not vaccinated. “The effect estimate was “even more pronounced” – a relative 74% reduction – when the risk of recurrence of CIN2+ was assessed for disease related to the two high-risk HPV types – HPV16 and HPV18,” explained the authors.

However, the researchers noted that these effects are unclear because of the “scarcity of data” and the “moderate to high overall risk of bias” of the available studies.
 

Quality of evidence inconclusive – more trials needed

With regards to CIN3, the risk of recurrence of was also reduced in patients who were vaccinated, but there was a high level of uncertainty about the quality of this evidence, cautioned the authors.

Evidence was also lacking on the benefit of HPV vaccination for recurrence of vulvar, vaginal, and anal lesions, as well as genital warts.

Analysis of the post-hoc studies from randomized controlled trial data with historic vaccination at randomization before the development of the disease reported inconsistent results, the authors said.

Several study limitations were acknowledged by the authors, including that most of the studies were observational, of low to moderate quality, and with relatively short follow-up times, which they pointed out prevented assessment of long-term effects. In addition, the average age of participants was not provided in most studies, and factors such as smoking – associated with a higher risk of recurrence – were not controlled for in many studies.

“HPV vaccination might reduce the risk of recurrence of CIN, in particular when related to HPV16 or HPV18, in women treated with local excision,” they concluded. However, they cautioned that “quality of evidence indicated that the data were inconclusive.”

“Large, appropriately powered, randomized controlled trials are required to establish the effectiveness of adjuvant HPV vaccination at the time of local surgical treatment of CIN,” they recommended.

“Given that the incidence of recurrence of high-grade disease is low in quality assured national screening programs, such as in the United Kingdom, absolute risks and a cost effectiveness analysis would be important in determining the implementation strategy of HPV vaccination after treatment,” the authors said.

Ms. Hughes said that the charity was pleased to see emerging research into the value of using the HPV vaccine to prevent the recurrence of cervical cell changes. She said that the charity looks forward to seeing “further large-scale studies into the effectiveness of this method.”

In the meantime, the charity encourages all women and other people with a cervix to attend their cervical screening and for young people to have the HPV vaccination when invited, as “these are the best tools we currently have to prevent cervical cancer,” she said.

A version of this article first appeared on Medscape UK.

Human papillomavirus (HPV) vaccine given around the time women have surgery for precancerous cervical lesions might lead to a reduction in the risk of lesions returning, as well as other HPV-related diseases, but the effects of this remain unclear.

The authors of the new study, published in The BMJ, explained that women who have been treated for high-grade cervical intra-epithelial neoplasia (CIN) have a “lifelong residual high risk of cervical cancer and other malignancies related to HPV infection,” and some research suggests that giving a preventive HPV vaccine alongside treatment for CIN might help to “reduce the risk in these women.”

HPV vaccination is highly effective at preventing the development of precancerous cervical lesions, CIN, and in the U.K., HPV vaccination is offered to girls and boys around the age of 12 or 13.

Eluned Hughes, head of information and engagement at Jo’s Cervical Cancer Trust, said: “Recent evidence has found that cases of cervical cancer have fallen 87% since the introduction of the HPV vaccine program in U.K. schools in 2008.”

“However, women over the age of 27, for whom the vaccine was not available, remain at increased risk of cervical cancer,” she highlighted.
 

Significant risk of bias and scarcity of data

In the study, researchers set out to explore the efficacy of HPV vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing local surgical treatment of preinvasive genital disease.

The systematic review and meta-analysis, led by researchers at Imperial College London, screened data from PubMed (Medline), Scopus, Cochrane, Web of Science, and ClinicalTrials.gov from inception to March 31, 2021.

The researchers analyzed the results of 18 studies – two randomized controlled trials (RCTs), 12 observational studies, and four post-hoc analyses of RCTs.

The authors said that the two RCTs were classified as low risk of bias, while in the observational studies and post-hoc analyses, risk of bias was moderate for seven, serious for seven, and critical for two. Average length of follow-up was 36 months.

There was a reduction of 57% in the risk of recurrence of high-grade pre-invasive disease (CIN2+) in individuals who were vaccinated, compared with those who were not vaccinated. “The effect estimate was “even more pronounced” – a relative 74% reduction – when the risk of recurrence of CIN2+ was assessed for disease related to the two high-risk HPV types – HPV16 and HPV18,” explained the authors.

However, the researchers noted that these effects are unclear because of the “scarcity of data” and the “moderate to high overall risk of bias” of the available studies.
 

Quality of evidence inconclusive – more trials needed

With regards to CIN3, the risk of recurrence of was also reduced in patients who were vaccinated, but there was a high level of uncertainty about the quality of this evidence, cautioned the authors.

Evidence was also lacking on the benefit of HPV vaccination for recurrence of vulvar, vaginal, and anal lesions, as well as genital warts.

Analysis of the post-hoc studies from randomized controlled trial data with historic vaccination at randomization before the development of the disease reported inconsistent results, the authors said.

Several study limitations were acknowledged by the authors, including that most of the studies were observational, of low to moderate quality, and with relatively short follow-up times, which they pointed out prevented assessment of long-term effects. In addition, the average age of participants was not provided in most studies, and factors such as smoking – associated with a higher risk of recurrence – were not controlled for in many studies.

“HPV vaccination might reduce the risk of recurrence of CIN, in particular when related to HPV16 or HPV18, in women treated with local excision,” they concluded. However, they cautioned that “quality of evidence indicated that the data were inconclusive.”

“Large, appropriately powered, randomized controlled trials are required to establish the effectiveness of adjuvant HPV vaccination at the time of local surgical treatment of CIN,” they recommended.

“Given that the incidence of recurrence of high-grade disease is low in quality assured national screening programs, such as in the United Kingdom, absolute risks and a cost effectiveness analysis would be important in determining the implementation strategy of HPV vaccination after treatment,” the authors said.

Ms. Hughes said that the charity was pleased to see emerging research into the value of using the HPV vaccine to prevent the recurrence of cervical cell changes. She said that the charity looks forward to seeing “further large-scale studies into the effectiveness of this method.”

In the meantime, the charity encourages all women and other people with a cervix to attend their cervical screening and for young people to have the HPV vaccination when invited, as “these are the best tools we currently have to prevent cervical cancer,” she said.

A version of this article first appeared on Medscape UK.

Human papillomavirus (HPV) vaccine given around the time women have surgery for precancerous cervical lesions might lead to a reduction in the risk of lesions returning, as well as other HPV-related diseases, but the effects of this remain unclear.

The authors of the new study, published in The BMJ, explained that women who have been treated for high-grade cervical intra-epithelial neoplasia (CIN) have a “lifelong residual high risk of cervical cancer and other malignancies related to HPV infection,” and some research suggests that giving a preventive HPV vaccine alongside treatment for CIN might help to “reduce the risk in these women.”

HPV vaccination is highly effective at preventing the development of precancerous cervical lesions, CIN, and in the U.K., HPV vaccination is offered to girls and boys around the age of 12 or 13.

Eluned Hughes, head of information and engagement at Jo’s Cervical Cancer Trust, said: “Recent evidence has found that cases of cervical cancer have fallen 87% since the introduction of the HPV vaccine program in U.K. schools in 2008.”

“However, women over the age of 27, for whom the vaccine was not available, remain at increased risk of cervical cancer,” she highlighted.
 

Significant risk of bias and scarcity of data

In the study, researchers set out to explore the efficacy of HPV vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing local surgical treatment of preinvasive genital disease.

The systematic review and meta-analysis, led by researchers at Imperial College London, screened data from PubMed (Medline), Scopus, Cochrane, Web of Science, and ClinicalTrials.gov from inception to March 31, 2021.

The researchers analyzed the results of 18 studies – two randomized controlled trials (RCTs), 12 observational studies, and four post-hoc analyses of RCTs.

The authors said that the two RCTs were classified as low risk of bias, while in the observational studies and post-hoc analyses, risk of bias was moderate for seven, serious for seven, and critical for two. Average length of follow-up was 36 months.

There was a reduction of 57% in the risk of recurrence of high-grade pre-invasive disease (CIN2+) in individuals who were vaccinated, compared with those who were not vaccinated. “The effect estimate was “even more pronounced” – a relative 74% reduction – when the risk of recurrence of CIN2+ was assessed for disease related to the two high-risk HPV types – HPV16 and HPV18,” explained the authors.

However, the researchers noted that these effects are unclear because of the “scarcity of data” and the “moderate to high overall risk of bias” of the available studies.
 

Quality of evidence inconclusive – more trials needed

With regards to CIN3, the risk of recurrence of was also reduced in patients who were vaccinated, but there was a high level of uncertainty about the quality of this evidence, cautioned the authors.

Evidence was also lacking on the benefit of HPV vaccination for recurrence of vulvar, vaginal, and anal lesions, as well as genital warts.

Analysis of the post-hoc studies from randomized controlled trial data with historic vaccination at randomization before the development of the disease reported inconsistent results, the authors said.

Several study limitations were acknowledged by the authors, including that most of the studies were observational, of low to moderate quality, and with relatively short follow-up times, which they pointed out prevented assessment of long-term effects. In addition, the average age of participants was not provided in most studies, and factors such as smoking – associated with a higher risk of recurrence – were not controlled for in many studies.

“HPV vaccination might reduce the risk of recurrence of CIN, in particular when related to HPV16 or HPV18, in women treated with local excision,” they concluded. However, they cautioned that “quality of evidence indicated that the data were inconclusive.”

“Large, appropriately powered, randomized controlled trials are required to establish the effectiveness of adjuvant HPV vaccination at the time of local surgical treatment of CIN,” they recommended.

“Given that the incidence of recurrence of high-grade disease is low in quality assured national screening programs, such as in the United Kingdom, absolute risks and a cost effectiveness analysis would be important in determining the implementation strategy of HPV vaccination after treatment,” the authors said.

Ms. Hughes said that the charity was pleased to see emerging research into the value of using the HPV vaccine to prevent the recurrence of cervical cell changes. She said that the charity looks forward to seeing “further large-scale studies into the effectiveness of this method.”

In the meantime, the charity encourages all women and other people with a cervix to attend their cervical screening and for young people to have the HPV vaccination when invited, as “these are the best tools we currently have to prevent cervical cancer,” she said.

A version of this article first appeared on Medscape UK.

In creating a guide about monkeypox for ob.gyns., Denise J. Jamieson, MD, MPH, turned to research she relied on during another outbreak of the disease nearly 20 years ago.

Dr. Jamieson, the James Robert McCord Professor and chair of the department of gynecology and obstetrics at Emory Healthcare, Atlanta, had been working for the Centers for Disease Control and Prevention in 2003 when doctors diagnosed monkeypox in several states.

That year, the virus was mainly transmitted by contact with pet prairie dogs, including in childcare and school settings. Of the approximately 70 suspected and confirmed cases, 55% occurred in female patients, according to one study .

Dr. Jamieson, an obstetrician with a focus on emerging infectious diseases, and colleagues at the agency published a commentary in Obstetrics & Gynecology highlighting the need for physicians to stay up to date with relevant information about the virus.

Fast forward to 2022: Dr. Jamieson – again with coauthors from the CDC – is delivering a similar message in the same journal about the need for clinicians to be prepared for this virus.

“Most ob.gyns. have never seen a case of monkeypox virus infection and may not be aware of testing, treatment, or pre-exposure or postexposure vaccine options,” she and her coauthors wrote in a primer published online.

But if a woman were to contract the virus, her ob.gyn. might well be the first clinician she called. “We are often the first people, the first physicians to see and evaluate women with various symptoms,” Dr. Jamieson said.

To promptly diagnose, treat, and prevent further spread of monkeypox, ob.gyns. need up-to-date information, Dr. Jamieson and colleagues said.

Based on data from related viruses like smallpox, monkeypox may be more severe in pregnant women and entail risk for adverse pregnancy outcomes, Dr. Jamieson said.
 

Outliers

So far this year, monkeypox has predominantly spread among men who have sex with men. Cases have occurred in women, however, some of whom have required hospitalization.

According to the CDC, as of July 25, 1,373 cases of monkeypox in the United States were in men and 13 in women. The total confirmed case count exceeded 5,800 as of Aug. 1. The agency recently announced that it planned to make the disease a reportable condition.

In the United Kingdom, which has been hit hard by the outbreak, researchers are keeping a close eye on the number of cases in women to assess how the disease is spreading.

At least one case of monkeypox in the United States has occurred in a pregnant woman who delivered. The mother and baby, who received immune globulin as a preventive measure, are doing well, according to health officials.  

“We know that infection can occur through placental transfer. In the case that we are aware of presently, it does not appear that the virus was transmitted,” said John T. Brooks, MD, the CDC’s chief medical officer in the division of HIV prevention, on a July 23 call with clinicians.

While monkeypox can be transmitted in utero and during sexual activity, it also can spread through any close contact with skin lesions or body fluids and possibly through touching contaminated items like clothing or linens, according to the CDC.
 

A preferred vaccine and antiviral in pregnancy

One monkeypox vaccine, Jynneos, is preferred for use during pregnancy, while another, ACAM2000, is contraindicated, the CDC advises.

Jynneos can be offered to people who are pregnant or breastfeeding who are eligible for vaccination based on confirmed or likely contact with cases, ideally within 4 days of exposure. People at high risk for exposure, such as laboratory workers, may receive the vaccine in advance.

Developmental toxicity studies in animals showed no evidence of harm with the Jynneos vaccine, Dr. Jamieson said.

ACAM2000, however, can cause fetal vaccinia and should not be used in people who are pregnant or breastfeeding, according to the CDC.

The Society for Maternal-Fetal Medicine notes that, if treatment for monkeypox is warranted, tecovirimat should be considered the first-line antiviral for pregnant, recently pregnant, and breastfeeding people, in line with CDC guidance.
 

Current outbreak ‘very different,’ but lessons apply

In 2003, some women exposed to monkeypox through contact with infected prairie dogs were pregnant – which is how Dr. Jamieson came to be involved in responding to the outbreak and studying the effects of the virus in pregnancy.

“When this resurfaced this year, of course it caught my attention,” Dr. Jamieson said. The extensive person-to-person transmission and far greater number of cases today make the current outbreak “very different” from the prior one, she said.

But key principles in managing the disease and understanding its potential risks in pregnancy – despite relatively limited information – remain the same.

“Whenever you are looking at an infectious disease, you want to think about, are pregnant persons more susceptible or more likely to have severe disease,” Dr. Jamieson said. Smallpox, a similar orthopoxvirus, “is more severe during pregnancy with a higher case fatality rate,” which is one reason for concern with monkeypox in this population.

In terms of pregnancy outcomes, researchers have data from only a handful of confirmed cases of monkeypox, which makes it difficult to draw conclusions, Dr. Jamieson said. A review of five cases from outside the United States in prior years found that three resulted in loss of the pregnancy. One resulted in preterm delivery of an infant who subsequently died. One child was apparently healthy and born at term.
 

Addition to the differential diagnosis

A separate team of researchers has proposed a clinical management algorithm for pregnant women with suspected exposure to monkeypox.

“Clinicians must maintain a high index of suspicion for monkeypox virus in any pregnant woman presenting with lymphadenopathy and vesiculopustular rash – including rash localized to the genital or perianal region – even if there are no apparent epidemiological links,” Pradip Dashraath, MBBS, National University Hospital, Singapore, and coauthors wrote in The Lancet.

Jamieson echoed the call for increased vigilance.

“As ob.gyns., people may present to us with genital lesions concerning for sexually transmitted infection. And it is important to include monkeypox in our differential,” Dr. Jamieson said. “We are trying to get the word out that it needs to be part of what you think about when you see a patient with genital ulcers.”

Health care professionals have acquired monkeypox through contact with patients or fomites, so clinicians should be sure to use appropriate precautions when evaluating patients who might have monkeypox, Dr. Jamieson added. Appropriate protective measures include wearing a gown, gloves, eye protection, and an N95.

A version of this article first appeared on Medscape.com.

In creating a guide about monkeypox for ob.gyns., Denise J. Jamieson, MD, MPH, turned to research she relied on during another outbreak of the disease nearly 20 years ago.

Dr. Jamieson, the James Robert McCord Professor and chair of the department of gynecology and obstetrics at Emory Healthcare, Atlanta, had been working for the Centers for Disease Control and Prevention in 2003 when doctors diagnosed monkeypox in several states.

That year, the virus was mainly transmitted by contact with pet prairie dogs, including in childcare and school settings. Of the approximately 70 suspected and confirmed cases, 55% occurred in female patients, according to one study .

Dr. Jamieson, an obstetrician with a focus on emerging infectious diseases, and colleagues at the agency published a commentary in Obstetrics & Gynecology highlighting the need for physicians to stay up to date with relevant information about the virus.

Fast forward to 2022: Dr. Jamieson – again with coauthors from the CDC – is delivering a similar message in the same journal about the need for clinicians to be prepared for this virus.

“Most ob.gyns. have never seen a case of monkeypox virus infection and may not be aware of testing, treatment, or pre-exposure or postexposure vaccine options,” she and her coauthors wrote in a primer published online.

But if a woman were to contract the virus, her ob.gyn. might well be the first clinician she called. “We are often the first people, the first physicians to see and evaluate women with various symptoms,” Dr. Jamieson said.

To promptly diagnose, treat, and prevent further spread of monkeypox, ob.gyns. need up-to-date information, Dr. Jamieson and colleagues said.

Based on data from related viruses like smallpox, monkeypox may be more severe in pregnant women and entail risk for adverse pregnancy outcomes, Dr. Jamieson said.
 

Outliers

So far this year, monkeypox has predominantly spread among men who have sex with men. Cases have occurred in women, however, some of whom have required hospitalization.

According to the CDC, as of July 25, 1,373 cases of monkeypox in the United States were in men and 13 in women. The total confirmed case count exceeded 5,800 as of Aug. 1. The agency recently announced that it planned to make the disease a reportable condition.

In the United Kingdom, which has been hit hard by the outbreak, researchers are keeping a close eye on the number of cases in women to assess how the disease is spreading.

At least one case of monkeypox in the United States has occurred in a pregnant woman who delivered. The mother and baby, who received immune globulin as a preventive measure, are doing well, according to health officials.  

“We know that infection can occur through placental transfer. In the case that we are aware of presently, it does not appear that the virus was transmitted,” said John T. Brooks, MD, the CDC’s chief medical officer in the division of HIV prevention, on a July 23 call with clinicians.

While monkeypox can be transmitted in utero and during sexual activity, it also can spread through any close contact with skin lesions or body fluids and possibly through touching contaminated items like clothing or linens, according to the CDC.
 

A preferred vaccine and antiviral in pregnancy

One monkeypox vaccine, Jynneos, is preferred for use during pregnancy, while another, ACAM2000, is contraindicated, the CDC advises.

Jynneos can be offered to people who are pregnant or breastfeeding who are eligible for vaccination based on confirmed or likely contact with cases, ideally within 4 days of exposure. People at high risk for exposure, such as laboratory workers, may receive the vaccine in advance.

Developmental toxicity studies in animals showed no evidence of harm with the Jynneos vaccine, Dr. Jamieson said.

ACAM2000, however, can cause fetal vaccinia and should not be used in people who are pregnant or breastfeeding, according to the CDC.

The Society for Maternal-Fetal Medicine notes that, if treatment for monkeypox is warranted, tecovirimat should be considered the first-line antiviral for pregnant, recently pregnant, and breastfeeding people, in line with CDC guidance.
 

Current outbreak ‘very different,’ but lessons apply

In 2003, some women exposed to monkeypox through contact with infected prairie dogs were pregnant – which is how Dr. Jamieson came to be involved in responding to the outbreak and studying the effects of the virus in pregnancy.

“When this resurfaced this year, of course it caught my attention,” Dr. Jamieson said. The extensive person-to-person transmission and far greater number of cases today make the current outbreak “very different” from the prior one, she said.

But key principles in managing the disease and understanding its potential risks in pregnancy – despite relatively limited information – remain the same.

“Whenever you are looking at an infectious disease, you want to think about, are pregnant persons more susceptible or more likely to have severe disease,” Dr. Jamieson said. Smallpox, a similar orthopoxvirus, “is more severe during pregnancy with a higher case fatality rate,” which is one reason for concern with monkeypox in this population.

In terms of pregnancy outcomes, researchers have data from only a handful of confirmed cases of monkeypox, which makes it difficult to draw conclusions, Dr. Jamieson said. A review of five cases from outside the United States in prior years found that three resulted in loss of the pregnancy. One resulted in preterm delivery of an infant who subsequently died. One child was apparently healthy and born at term.
 

Addition to the differential diagnosis

A separate team of researchers has proposed a clinical management algorithm for pregnant women with suspected exposure to monkeypox.

“Clinicians must maintain a high index of suspicion for monkeypox virus in any pregnant woman presenting with lymphadenopathy and vesiculopustular rash – including rash localized to the genital or perianal region – even if there are no apparent epidemiological links,” Pradip Dashraath, MBBS, National University Hospital, Singapore, and coauthors wrote in The Lancet.

Jamieson echoed the call for increased vigilance.

“As ob.gyns., people may present to us with genital lesions concerning for sexually transmitted infection. And it is important to include monkeypox in our differential,” Dr. Jamieson said. “We are trying to get the word out that it needs to be part of what you think about when you see a patient with genital ulcers.”

Health care professionals have acquired monkeypox through contact with patients or fomites, so clinicians should be sure to use appropriate precautions when evaluating patients who might have monkeypox, Dr. Jamieson added. Appropriate protective measures include wearing a gown, gloves, eye protection, and an N95.

A version of this article first appeared on Medscape.com.

In creating a guide about monkeypox for ob.gyns., Denise J. Jamieson, MD, MPH, turned to research she relied on during another outbreak of the disease nearly 20 years ago.

Dr. Jamieson, the James Robert McCord Professor and chair of the department of gynecology and obstetrics at Emory Healthcare, Atlanta, had been working for the Centers for Disease Control and Prevention in 2003 when doctors diagnosed monkeypox in several states.

That year, the virus was mainly transmitted by contact with pet prairie dogs, including in childcare and school settings. Of the approximately 70 suspected and confirmed cases, 55% occurred in female patients, according to one study .

Dr. Jamieson, an obstetrician with a focus on emerging infectious diseases, and colleagues at the agency published a commentary in Obstetrics & Gynecology highlighting the need for physicians to stay up to date with relevant information about the virus.

Fast forward to 2022: Dr. Jamieson – again with coauthors from the CDC – is delivering a similar message in the same journal about the need for clinicians to be prepared for this virus.

“Most ob.gyns. have never seen a case of monkeypox virus infection and may not be aware of testing, treatment, or pre-exposure or postexposure vaccine options,” she and her coauthors wrote in a primer published online.

But if a woman were to contract the virus, her ob.gyn. might well be the first clinician she called. “We are often the first people, the first physicians to see and evaluate women with various symptoms,” Dr. Jamieson said.

To promptly diagnose, treat, and prevent further spread of monkeypox, ob.gyns. need up-to-date information, Dr. Jamieson and colleagues said.

Based on data from related viruses like smallpox, monkeypox may be more severe in pregnant women and entail risk for adverse pregnancy outcomes, Dr. Jamieson said.
 

Outliers

So far this year, monkeypox has predominantly spread among men who have sex with men. Cases have occurred in women, however, some of whom have required hospitalization.

According to the CDC, as of July 25, 1,373 cases of monkeypox in the United States were in men and 13 in women. The total confirmed case count exceeded 5,800 as of Aug. 1. The agency recently announced that it planned to make the disease a reportable condition.

In the United Kingdom, which has been hit hard by the outbreak, researchers are keeping a close eye on the number of cases in women to assess how the disease is spreading.

At least one case of monkeypox in the United States has occurred in a pregnant woman who delivered. The mother and baby, who received immune globulin as a preventive measure, are doing well, according to health officials.  

“We know that infection can occur through placental transfer. In the case that we are aware of presently, it does not appear that the virus was transmitted,” said John T. Brooks, MD, the CDC’s chief medical officer in the division of HIV prevention, on a July 23 call with clinicians.

While monkeypox can be transmitted in utero and during sexual activity, it also can spread through any close contact with skin lesions or body fluids and possibly through touching contaminated items like clothing or linens, according to the CDC.
 

A preferred vaccine and antiviral in pregnancy

One monkeypox vaccine, Jynneos, is preferred for use during pregnancy, while another, ACAM2000, is contraindicated, the CDC advises.

Jynneos can be offered to people who are pregnant or breastfeeding who are eligible for vaccination based on confirmed or likely contact with cases, ideally within 4 days of exposure. People at high risk for exposure, such as laboratory workers, may receive the vaccine in advance.

Developmental toxicity studies in animals showed no evidence of harm with the Jynneos vaccine, Dr. Jamieson said.

ACAM2000, however, can cause fetal vaccinia and should not be used in people who are pregnant or breastfeeding, according to the CDC.

The Society for Maternal-Fetal Medicine notes that, if treatment for monkeypox is warranted, tecovirimat should be considered the first-line antiviral for pregnant, recently pregnant, and breastfeeding people, in line with CDC guidance.
 

Current outbreak ‘very different,’ but lessons apply

In 2003, some women exposed to monkeypox through contact with infected prairie dogs were pregnant – which is how Dr. Jamieson came to be involved in responding to the outbreak and studying the effects of the virus in pregnancy.

“When this resurfaced this year, of course it caught my attention,” Dr. Jamieson said. The extensive person-to-person transmission and far greater number of cases today make the current outbreak “very different” from the prior one, she said.

But key principles in managing the disease and understanding its potential risks in pregnancy – despite relatively limited information – remain the same.

“Whenever you are looking at an infectious disease, you want to think about, are pregnant persons more susceptible or more likely to have severe disease,” Dr. Jamieson said. Smallpox, a similar orthopoxvirus, “is more severe during pregnancy with a higher case fatality rate,” which is one reason for concern with monkeypox in this population.

In terms of pregnancy outcomes, researchers have data from only a handful of confirmed cases of monkeypox, which makes it difficult to draw conclusions, Dr. Jamieson said. A review of five cases from outside the United States in prior years found that three resulted in loss of the pregnancy. One resulted in preterm delivery of an infant who subsequently died. One child was apparently healthy and born at term.
 

Addition to the differential diagnosis

A separate team of researchers has proposed a clinical management algorithm for pregnant women with suspected exposure to monkeypox.

“Clinicians must maintain a high index of suspicion for monkeypox virus in any pregnant woman presenting with lymphadenopathy and vesiculopustular rash – including rash localized to the genital or perianal region – even if there are no apparent epidemiological links,” Pradip Dashraath, MBBS, National University Hospital, Singapore, and coauthors wrote in The Lancet.

Jamieson echoed the call for increased vigilance.

“As ob.gyns., people may present to us with genital lesions concerning for sexually transmitted infection. And it is important to include monkeypox in our differential,” Dr. Jamieson said. “We are trying to get the word out that it needs to be part of what you think about when you see a patient with genital ulcers.”

Health care professionals have acquired monkeypox through contact with patients or fomites, so clinicians should be sure to use appropriate precautions when evaluating patients who might have monkeypox, Dr. Jamieson added. Appropriate protective measures include wearing a gown, gloves, eye protection, and an N95.

A version of this article first appeared on Medscape.com.

A new study sheds light on some of the risk factors for the development of psychosis, including the potentially causative role of sexual assault.

Investigators conducted an exposome-wide association analysis on more than 155,000 individuals. Of more than 140 correlates of psychotic experiences that they identified, they narrowed it down to 36 variables, which they further explored using Mendelian randomization analysis.

The analysis found that having been the victim of a sexual assault might be a potential causal risk factor for psychotic experiences. On the other hand, having experienced a physical violent crime, cannabis use, and prolonged worry after embarrassment showed a pleiotropic association and appeared to be an aftereffect of psychotic experience.

“From a public health perspective, we need more investment in comprehensive strategies to prevent traumatic experiences at the population level to decrease the burden of psychosis,” senior author Sinan Gülöksüz, MD, PhD, associate professor in the department of psychiatry and neuropsychiatry, Maastricht University Medical Center, the Netherlands, said in an interview.

“From a clinical perspective, clinicians should be aware of the harmful influence of traumatic experiences on mental health and address this through interventions such as trauma-informed care,” he said.

The study was published online in JAMA Psychiatry.

‘Disentangling’ cause and effect

“Previous research has shown associations between psychosis and a few environmental factors, such as substance use, urbanicity, pregnancy complications, and traumatic experiences, but research has so far investigated only a few specific environmental factors by singling them out in individual studies,” Dr. Gülöksüz said.

“Yet, environment is a much more complex and interactive network that includes many factors shaping our health – where we live, what we eat, our lifestyle preferences and habits such as exercise and smoking, and our social surrounding,” he continued. “Rarely has it been possible to understand whether these environmental factors have causal roles in developing psychosis.”

To investigate the question, the researchers turned to the UK Biobank, one of the largest population-based datasets in the world. The current study focused on individuals with completed data on mental questionnaires that assessed psychotic experiences (n = 155,247; mean [SD] age, 55.94 [7.74] years; 57% female).

They began by conducting an exposome-wide association study, using logistic regression analyses with psychotic experiences as the outcome and adjusting all analyses for age and sex.

“Initially, we identified many associations between environmental factors and psychotic experiences in this large cohort,” Dr. Gülöksüz reported.

In the final multivariable model, variables associated with psychotic experiences were further analyzed using “genetically informed approaches to probe potential associations.”

The researchers utilized Mendelian randomization (MR) methodology “to disentangle cause and effect in this observational study,” Dr. Gülöksüz said. “This method reduces confounding and reverse causation in observational studies by using genetic variants that have been passed on from generation to generation randomly as instruments.”

MR analysis “has allowed us to assess whether these associations reflect potentially causal influences of environmental factors on psychotic experiences,” he added.
 

Well-studied and unexplored risk factors

The researchers identified 162 variables associated with psychotic experiences in the discovery dataset and were able to replicate 148. When these 148 variables were subjected to multivariable analyses, 36 were found to be statistically significantly associated with psychotic experiences. Of these variables, 28 had “significant genetic overlap” with psychotic experiences.

When the researchers conducted one-sample MR analyses, they found forward associations with three variables and reverse associations with three variables.

Forward associations were found with ever having experienced sexual assault (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.14-1.52; P = 2.67), and forward associations (with pleiotropy) were found with ever having experienced a physically violent crime and risk-taking behavior (OR, 1.25, 95% CI, 1.11-1.41; P = 3.28 and OR, 1.21, 95% CI, 1.08-1.35; P = 1.34, respectively).

“The allele scores for these 3 variables explained 0.03% to 0.23% variance of the corresponding variable” and the F statistics “ranged from 21.53 to 181.84, indicating that the results did not suffer from a weak-instrument bias,” the authors reported.

The researchers calculated an instrument based on increasing psychotic experiences risk allele scores and found that these scores explained 0.14% variance of psychotic experiences (F statistic, 19.26).

Using that calculation, they found a reverse association with having experienced a physically violent crime (OR, 1.08; 95% CI, 1.04-1.13; P = 3.92 × 10-4), cannabis use (OR, 1.11; 95% CI, 1.06-1.15; P = 2.64 × 10-6), and worrying too long after embarrassment (OR, 1.06; 95% CI, 1.03-1.10; P = 3.96 × 10-4). They then validated these associations.

The presence of all five correlates was associated with tenfold increased odds of psychotic experiences (OR, 10.63; 95% CI, 8.27-13.65, P = 1.2 × 10-114).

“Associations with psychotic experiences were found with both well-studied and unexplored multiple correlated variables,” the authors stated.
 

Era of ‘big data’

In a comment, Chirag Patel, PhD, associate professor of biomedical informatics at Harvard Medical School, Boston, who was not involved with the study, said he thought the study was “a nice example of a data-driven and comprehensive study of the environment coupled with attempts to triangulate evidence from genetics, made possible by biobank data.

“To guide public health policies and implementation of prevention strategies for psychosis, we need more systematic analyses and triangulate evidence with genetically informed methods to identify potentially modifiable risk factors in the era of ‘big data,’ ” he said.

“For instance, traumatic experiences contribute to poor mental and physical health, including psychosis,” Dr. Gülöksüz added.

The Kootstra Talent Fellowship, the Ophelia Research Project, and the Vidi Award from the Netherlands Scientific Organization provided funding to individual investigators. Dr. Gülöksüz and coauthors declared no relevant financial conflicts. Dr. Patel served as a reviewer on the study.

A version of this article first appeared on Medscape.com.

A new study sheds light on some of the risk factors for the development of psychosis, including the potentially causative role of sexual assault.

Investigators conducted an exposome-wide association analysis on more than 155,000 individuals. Of more than 140 correlates of psychotic experiences that they identified, they narrowed it down to 36 variables, which they further explored using Mendelian randomization analysis.

The analysis found that having been the victim of a sexual assault might be a potential causal risk factor for psychotic experiences. On the other hand, having experienced a physical violent crime, cannabis use, and prolonged worry after embarrassment showed a pleiotropic association and appeared to be an aftereffect of psychotic experience.

“From a public health perspective, we need more investment in comprehensive strategies to prevent traumatic experiences at the population level to decrease the burden of psychosis,” senior author Sinan Gülöksüz, MD, PhD, associate professor in the department of psychiatry and neuropsychiatry, Maastricht University Medical Center, the Netherlands, said in an interview.

“From a clinical perspective, clinicians should be aware of the harmful influence of traumatic experiences on mental health and address this through interventions such as trauma-informed care,” he said.

The study was published online in JAMA Psychiatry.

‘Disentangling’ cause and effect

“Previous research has shown associations between psychosis and a few environmental factors, such as substance use, urbanicity, pregnancy complications, and traumatic experiences, but research has so far investigated only a few specific environmental factors by singling them out in individual studies,” Dr. Gülöksüz said.

“Yet, environment is a much more complex and interactive network that includes many factors shaping our health – where we live, what we eat, our lifestyle preferences and habits such as exercise and smoking, and our social surrounding,” he continued. “Rarely has it been possible to understand whether these environmental factors have causal roles in developing psychosis.”

To investigate the question, the researchers turned to the UK Biobank, one of the largest population-based datasets in the world. The current study focused on individuals with completed data on mental questionnaires that assessed psychotic experiences (n = 155,247; mean [SD] age, 55.94 [7.74] years; 57% female).

They began by conducting an exposome-wide association study, using logistic regression analyses with psychotic experiences as the outcome and adjusting all analyses for age and sex.

“Initially, we identified many associations between environmental factors and psychotic experiences in this large cohort,” Dr. Gülöksüz reported.

In the final multivariable model, variables associated with psychotic experiences were further analyzed using “genetically informed approaches to probe potential associations.”

The researchers utilized Mendelian randomization (MR) methodology “to disentangle cause and effect in this observational study,” Dr. Gülöksüz said. “This method reduces confounding and reverse causation in observational studies by using genetic variants that have been passed on from generation to generation randomly as instruments.”

MR analysis “has allowed us to assess whether these associations reflect potentially causal influences of environmental factors on psychotic experiences,” he added.
 

Well-studied and unexplored risk factors

The researchers identified 162 variables associated with psychotic experiences in the discovery dataset and were able to replicate 148. When these 148 variables were subjected to multivariable analyses, 36 were found to be statistically significantly associated with psychotic experiences. Of these variables, 28 had “significant genetic overlap” with psychotic experiences.

When the researchers conducted one-sample MR analyses, they found forward associations with three variables and reverse associations with three variables.

Forward associations were found with ever having experienced sexual assault (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.14-1.52; P = 2.67), and forward associations (with pleiotropy) were found with ever having experienced a physically violent crime and risk-taking behavior (OR, 1.25, 95% CI, 1.11-1.41; P = 3.28 and OR, 1.21, 95% CI, 1.08-1.35; P = 1.34, respectively).

“The allele scores for these 3 variables explained 0.03% to 0.23% variance of the corresponding variable” and the F statistics “ranged from 21.53 to 181.84, indicating that the results did not suffer from a weak-instrument bias,” the authors reported.

The researchers calculated an instrument based on increasing psychotic experiences risk allele scores and found that these scores explained 0.14% variance of psychotic experiences (F statistic, 19.26).

Using that calculation, they found a reverse association with having experienced a physically violent crime (OR, 1.08; 95% CI, 1.04-1.13; P = 3.92 × 10-4), cannabis use (OR, 1.11; 95% CI, 1.06-1.15; P = 2.64 × 10-6), and worrying too long after embarrassment (OR, 1.06; 95% CI, 1.03-1.10; P = 3.96 × 10-4). They then validated these associations.

The presence of all five correlates was associated with tenfold increased odds of psychotic experiences (OR, 10.63; 95% CI, 8.27-13.65, P = 1.2 × 10-114).

“Associations with psychotic experiences were found with both well-studied and unexplored multiple correlated variables,” the authors stated.
 

Era of ‘big data’

In a comment, Chirag Patel, PhD, associate professor of biomedical informatics at Harvard Medical School, Boston, who was not involved with the study, said he thought the study was “a nice example of a data-driven and comprehensive study of the environment coupled with attempts to triangulate evidence from genetics, made possible by biobank data.

“To guide public health policies and implementation of prevention strategies for psychosis, we need more systematic analyses and triangulate evidence with genetically informed methods to identify potentially modifiable risk factors in the era of ‘big data,’ ” he said.

“For instance, traumatic experiences contribute to poor mental and physical health, including psychosis,” Dr. Gülöksüz added.

The Kootstra Talent Fellowship, the Ophelia Research Project, and the Vidi Award from the Netherlands Scientific Organization provided funding to individual investigators. Dr. Gülöksüz and coauthors declared no relevant financial conflicts. Dr. Patel served as a reviewer on the study.

A version of this article first appeared on Medscape.com.

A new study sheds light on some of the risk factors for the development of psychosis, including the potentially causative role of sexual assault.

Investigators conducted an exposome-wide association analysis on more than 155,000 individuals. Of more than 140 correlates of psychotic experiences that they identified, they narrowed it down to 36 variables, which they further explored using Mendelian randomization analysis.

The analysis found that having been the victim of a sexual assault might be a potential causal risk factor for psychotic experiences. On the other hand, having experienced a physical violent crime, cannabis use, and prolonged worry after embarrassment showed a pleiotropic association and appeared to be an aftereffect of psychotic experience.

“From a public health perspective, we need more investment in comprehensive strategies to prevent traumatic experiences at the population level to decrease the burden of psychosis,” senior author Sinan Gülöksüz, MD, PhD, associate professor in the department of psychiatry and neuropsychiatry, Maastricht University Medical Center, the Netherlands, said in an interview.

“From a clinical perspective, clinicians should be aware of the harmful influence of traumatic experiences on mental health and address this through interventions such as trauma-informed care,” he said.

The study was published online in JAMA Psychiatry.

‘Disentangling’ cause and effect

“Previous research has shown associations between psychosis and a few environmental factors, such as substance use, urbanicity, pregnancy complications, and traumatic experiences, but research has so far investigated only a few specific environmental factors by singling them out in individual studies,” Dr. Gülöksüz said.

“Yet, environment is a much more complex and interactive network that includes many factors shaping our health – where we live, what we eat, our lifestyle preferences and habits such as exercise and smoking, and our social surrounding,” he continued. “Rarely has it been possible to understand whether these environmental factors have causal roles in developing psychosis.”

To investigate the question, the researchers turned to the UK Biobank, one of the largest population-based datasets in the world. The current study focused on individuals with completed data on mental questionnaires that assessed psychotic experiences (n = 155,247; mean [SD] age, 55.94 [7.74] years; 57% female).

They began by conducting an exposome-wide association study, using logistic regression analyses with psychotic experiences as the outcome and adjusting all analyses for age and sex.

“Initially, we identified many associations between environmental factors and psychotic experiences in this large cohort,” Dr. Gülöksüz reported.

In the final multivariable model, variables associated with psychotic experiences were further analyzed using “genetically informed approaches to probe potential associations.”

The researchers utilized Mendelian randomization (MR) methodology “to disentangle cause and effect in this observational study,” Dr. Gülöksüz said. “This method reduces confounding and reverse causation in observational studies by using genetic variants that have been passed on from generation to generation randomly as instruments.”

MR analysis “has allowed us to assess whether these associations reflect potentially causal influences of environmental factors on psychotic experiences,” he added.
 

Well-studied and unexplored risk factors

The researchers identified 162 variables associated with psychotic experiences in the discovery dataset and were able to replicate 148. When these 148 variables were subjected to multivariable analyses, 36 were found to be statistically significantly associated with psychotic experiences. Of these variables, 28 had “significant genetic overlap” with psychotic experiences.

When the researchers conducted one-sample MR analyses, they found forward associations with three variables and reverse associations with three variables.

Forward associations were found with ever having experienced sexual assault (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.14-1.52; P = 2.67), and forward associations (with pleiotropy) were found with ever having experienced a physically violent crime and risk-taking behavior (OR, 1.25, 95% CI, 1.11-1.41; P = 3.28 and OR, 1.21, 95% CI, 1.08-1.35; P = 1.34, respectively).

“The allele scores for these 3 variables explained 0.03% to 0.23% variance of the corresponding variable” and the F statistics “ranged from 21.53 to 181.84, indicating that the results did not suffer from a weak-instrument bias,” the authors reported.

The researchers calculated an instrument based on increasing psychotic experiences risk allele scores and found that these scores explained 0.14% variance of psychotic experiences (F statistic, 19.26).

Using that calculation, they found a reverse association with having experienced a physically violent crime (OR, 1.08; 95% CI, 1.04-1.13; P = 3.92 × 10-4), cannabis use (OR, 1.11; 95% CI, 1.06-1.15; P = 2.64 × 10-6), and worrying too long after embarrassment (OR, 1.06; 95% CI, 1.03-1.10; P = 3.96 × 10-4). They then validated these associations.

The presence of all five correlates was associated with tenfold increased odds of psychotic experiences (OR, 10.63; 95% CI, 8.27-13.65, P = 1.2 × 10-114).

“Associations with psychotic experiences were found with both well-studied and unexplored multiple correlated variables,” the authors stated.
 

Era of ‘big data’

In a comment, Chirag Patel, PhD, associate professor of biomedical informatics at Harvard Medical School, Boston, who was not involved with the study, said he thought the study was “a nice example of a data-driven and comprehensive study of the environment coupled with attempts to triangulate evidence from genetics, made possible by biobank data.

“To guide public health policies and implementation of prevention strategies for psychosis, we need more systematic analyses and triangulate evidence with genetically informed methods to identify potentially modifiable risk factors in the era of ‘big data,’ ” he said.

“For instance, traumatic experiences contribute to poor mental and physical health, including psychosis,” Dr. Gülöksüz added.

The Kootstra Talent Fellowship, the Ophelia Research Project, and the Vidi Award from the Netherlands Scientific Organization provided funding to individual investigators. Dr. Gülöksüz and coauthors declared no relevant financial conflicts. Dr. Patel served as a reviewer on the study.

A version of this article first appeared on Medscape.com.

After the US Supreme Court overturned Roe v Wade in June, Gilbert R. Cisneros Jr., Under Secretary of Defense for Personnel and Readiness, released a memo on “Ensuring Access to Essential Women’s Health Care Services for Service Members, Dependents, Beneficiaries, and Department of Defense Civilian Employees.” In the memo, Cisneros clarified the US Department of Defense (DoD) policies and emphasized, “There will be no interruption to this care.”

Covered abortions—instances where the life of the mother would be endangered if the fetus were carried to term, or when the pregnancy is the result of rape or incest—are still covered. Health care professionals will continue to follow this policy and military medical facilities leadership will implement measures to ensure continued access to care.

The implications of the Supreme Court decision are complicated, Cisneros said. “It is the Department of Justice’s longstanding position that States generally may not impose criminal or civil liability on federal employees who perform their duties in a manner authorized by federal law,” the memo continues. “We will work with the Department of Justice to ensure access to counsel for such civilian employees and Service members if needed and as appropriate.”

The decision also does not affect the DoD’s existing leave policies, which authorize active-duty service members to travel as necessary to receive abortion care. The travel may be government-funded official travel for a covered abortion, or for all other cases, may be undertaken as regular leave at the service member’s expense. DoD civilian employees may continue to use sick leave or other forms of leave to care for themselves or their family members. Sick leave may be used to cover travel to obtain any type of medical treatment.

The Court’s decision “will have significant implications,” Cisneros wrote, adding, “As Secretary Austin has made clear, nothing is more important than the health and well-being of our Service members, the civilian workforce, and DoD families, and we are committed to taking care of all our people and ensuring that the entire Force remains ready and resilient.”

After the US Supreme Court overturned Roe v Wade in June, Gilbert R. Cisneros Jr., Under Secretary of Defense for Personnel and Readiness, released a memo on “Ensuring Access to Essential Women’s Health Care Services for Service Members, Dependents, Beneficiaries, and Department of Defense Civilian Employees.” In the memo, Cisneros clarified the US Department of Defense (DoD) policies and emphasized, “There will be no interruption to this care.”

Covered abortions—instances where the life of the mother would be endangered if the fetus were carried to term, or when the pregnancy is the result of rape or incest—are still covered. Health care professionals will continue to follow this policy and military medical facilities leadership will implement measures to ensure continued access to care.

The implications of the Supreme Court decision are complicated, Cisneros said. “It is the Department of Justice’s longstanding position that States generally may not impose criminal or civil liability on federal employees who perform their duties in a manner authorized by federal law,” the memo continues. “We will work with the Department of Justice to ensure access to counsel for such civilian employees and Service members if needed and as appropriate.”

The decision also does not affect the DoD’s existing leave policies, which authorize active-duty service members to travel as necessary to receive abortion care. The travel may be government-funded official travel for a covered abortion, or for all other cases, may be undertaken as regular leave at the service member’s expense. DoD civilian employees may continue to use sick leave or other forms of leave to care for themselves or their family members. Sick leave may be used to cover travel to obtain any type of medical treatment.

The Court’s decision “will have significant implications,” Cisneros wrote, adding, “As Secretary Austin has made clear, nothing is more important than the health and well-being of our Service members, the civilian workforce, and DoD families, and we are committed to taking care of all our people and ensuring that the entire Force remains ready and resilient.”

After the US Supreme Court overturned Roe v Wade in June, Gilbert R. Cisneros Jr., Under Secretary of Defense for Personnel and Readiness, released a memo on “Ensuring Access to Essential Women’s Health Care Services for Service Members, Dependents, Beneficiaries, and Department of Defense Civilian Employees.” In the memo, Cisneros clarified the US Department of Defense (DoD) policies and emphasized, “There will be no interruption to this care.”

Covered abortions—instances where the life of the mother would be endangered if the fetus were carried to term, or when the pregnancy is the result of rape or incest—are still covered. Health care professionals will continue to follow this policy and military medical facilities leadership will implement measures to ensure continued access to care.

The implications of the Supreme Court decision are complicated, Cisneros said. “It is the Department of Justice’s longstanding position that States generally may not impose criminal or civil liability on federal employees who perform their duties in a manner authorized by federal law,” the memo continues. “We will work with the Department of Justice to ensure access to counsel for such civilian employees and Service members if needed and as appropriate.”

The decision also does not affect the DoD’s existing leave policies, which authorize active-duty service members to travel as necessary to receive abortion care. The travel may be government-funded official travel for a covered abortion, or for all other cases, may be undertaken as regular leave at the service member’s expense. DoD civilian employees may continue to use sick leave or other forms of leave to care for themselves or their family members. Sick leave may be used to cover travel to obtain any type of medical treatment.

The Court’s decision “will have significant implications,” Cisneros wrote, adding, “As Secretary Austin has made clear, nothing is more important than the health and well-being of our Service members, the civilian workforce, and DoD families, and we are committed to taking care of all our people and ensuring that the entire Force remains ready and resilient.”

Study 1 Overview (Cortés et al)

Objective: To compare the efficacy and safety of trastuzumab deruxtecan with those of trastuzumab emtansine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and taxane.

Design: Phase 3, multicenter, open-label randomized trial conducted at 169 centers and 15 countries.

Setting and participants: Eligible patients had to have unresectable or metastatic HER2-positive breast cancer that had progressed during or after treatment with trastuzumab and a taxane or had disease that progressed within 6 months after neoadjuvant or adjuvant treatment involving trastuzumab or taxane. Patients with stable or previously treated brain metastases were eligible. Patients were not eligible for the study if they had symptomatic brain metastases, prior exposure to trastuzumab emtansine, or a history of interstitial lung disease.

Intervention: Patients were randomized in a 1-to-1 fashion to receive either trastuzumab deruxtecan 5.4 mg/kg every 3 weeks or trastuzumab emtansine 3.6 mg/kg every 3 weeks. Patients were stratified according to hormone-receptor status, prior treatment with epratuzumab, and the presence or absence of visceral disease.

Main outcome measures: The primary endpoint of the study was progression-free survival as determined by an independent central review. Secondary endpoints included overall survival, overall response, and safety.

Main results: A total of 524 patients were enrolled in the study, with 261 patients randomized to trastuzumab deruxtecan and 263 patients randomized to trastuzumab emtansine. The demographic and baseline characteristics were similar between the 2 cohorts, and 60% of patients in both groups received prior epratuzumab therapy. Stable brain metastases were present in around 20% of patients in each group, and 70% of patients in each group had visceral disease. The median duration of follow-up was 16.2 months with trastuzumab deruxtecan and 15.3 months with trastuzumab emtansine.

The median progression-free survival was not reached in the trastuzumab deruxtecan group and was 6.8 months in the trastuzumab emtansine group (95% CI, 5.6-8.2). At 12 months the percentage of patients alive without disease progression was significantly larger in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group. The hazard ratio for disease progression or death from any cause was 0.28 (95% CI, 0.22-0.37; P < .001). Subgroup analyses showed a benefit in progression-free survival with trastuzumab deruxtecan across all subgroups.

At the time of this analysis, the percentage of patients who were alive at 12 months was 94% with trastuzumab deruxtecan and 85.9% with trastuzumab emtansine. The response rates were significantly higher with trastuzumab deruxtecan compared with trastuzumab emtansine (79.7% vs 34.2%). A complete response was seen in 16% of patients in the trastuzumab deruxtecan arm, compared with 8.7% of patients in the trastuzumab emtansine group. The disease control rate (complete response, partial response, or stable disease) was higher in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group (96.6% vs 76.8%).

Serious adverse events were reported in 19% of patients in the trastuzumab deruxtecan group and 18% of patients in the trastuzumab emtansine group. Discontinuation due to adverse events was higher in the trastuzumab deruxtecan group, with 13.6% of patients discontinuing trastuzumab deruxtecan. Grade 3 or higher adverse events were seen in 52% of patients treated with trastuzumab deruxtecan and 48% of patients treated with trastuzumab emtansine. The most commonly reported adverse event with trastuzumab deruxtecan was nausea/vomiting and fatigue. These adverse events were seen more in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group. No drug-related grade 5 adverse events were reported.

In the trastuzumab deruxtecan group, 10.5% of patients receiving trastuzumab deruxtecan developed interstitial lung disease or pneumonitis. Seven patients had grade 1 events, 18 patients had grade 2 events, and 2 patients had grade 3 events. No grade 4 or 5 events were noted in either treatment group. The median time to onset of interstitial lung disease or pneumonitis in those receiving trastuzumab deruxtecan was 168 days (range, 33-507). Discontinuation of therapy due to interstitial lung disease or pneumonitis occurred in 8% of patients receiving trastuzumab deruxtecan and 1% of patients receiving trastuzumab emtansine.

Conclusion: Trastuzumab deruxtecan significantly decreases the risk of disease progression or death compared to trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who have progressed on prior trastuzumab and taxane-based therapy.

Study 2 Overview (Modi et al)

Objective: To assess the efficacy of trastuzumab deruxtecan in patients with unresectable or metastatic breast cancer with low levels of HER2 expression.

Design: This was a randomized, 2-group, open-label, phase 3 trial.

Setting and participants: The trial was designed with a planned enrollment of 480 patients with hormone receptor–positive disease and 60 patients with hormone receptor–negative disease. Patients were randomized in a 2:1 ratio. Randomization was stratified according to HER2 status (immunohistochemical [IHC] 1+ vs IHC 2+/in situ hybridization [ISH] negative), number of prior lines of therapy, and hormone-receptor status. IHC scores for HER2 expression were determined through central testing. Specimens that had HER2 IHC scores of 2+ were reflexed to ISH. Specimens were considered HER2-low-expressing if they had an IHC score of 1+ or if they had an IHC score of 2+ and were ISH negative.

Eligible patients had to have received chemotherapy for metastatic disease or had disease recurrence during or within 6 months after completing adjuvant chemotherapy. Patients with hormone receptor–positive disease must have had at least 1 line of endocrine therapy. Patients were eligible if they had stable brain metastases. Patients with interstitial lung disease were excluded.

Intervention: Patients were randomized to receive trastuzumab deruxtecan 5.4 mg/kg every 3 weeks or physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel).

Main outcome measures: The primary endpoint was progression-free survival in patients with hormone receptor–positive disease. Secondary endpoints were progression-free survival among all patients, overall survival in hormone receptor–positive patients, and overall survival in all patients. Additional secondary endpoints included objective response rates, duration of response, and efficacy in hormone receptor–negative patients.

Main results: A total of 373 patients were assigned to the trastuzumab deruxtecan group and 184 patients were assigned to the physician’s choice chemotherapy group; 88% of patients in each cohort were hormone receptor–positive. In the physician’s choice chemotherapy group, 51% received eribulin, 20% received capecitabine, 10% received nab-paclitaxel, 10% received gemcitabine, and 8% received paclitaxel. The demographic and baseline characteristics were similar between both cohorts. The median duration of follow-up was 18.4 months.

The median progression-free survival in the hormone receptor–positive cohort was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician’s choice chemotherapy group (HR, 0.51; 95% CI, 0.4-0.64). Subgroup analyses revealed a benefit across all subgroups. The median progression-free survival among patients with a HER2 IHC score of 1+ and those with a HER2 IHC score of 2+/negative ISH were identical. In patients who received a prior CDK 4/6 inhibitor, the median progression-free survival was also 10 months in the trastuzumab deruxtecan group. In those who were CDK 4/6- naïve, the progression-free survival was 11.7 months. The progression-free survival in all patients was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice chemotherapy group (HR, 0.46; 95% CI, 0.24-0.89).

The median overall survival in the hormone receptor–positive cohort was 23.9 months in the trastuzumab deruxtecan group compared with 17.5 months in the physician’s choice chemotherapy group (HR, 0.64; 95% CI, 0.48-0.86; P = .003). The median overall survival in the entire population was 23.4 months in the trastuzumab deruxtecan group vs 16.8 months in the physician’s choice chemotherapy group. In the hormone receptor–negative cohort, the median overall survival was 18.2 months in the trastuzumab deruxtecan group and 8.3 months in the physician’s choice chemotherapy group. Complete responses were seen in 3.6% in the trastuzumab deruxtecan group and 0.6% and the physician’s choice chemotherapy group. The median duration of response was 10.7 months in the trastuzumab deruxtecan group and 6.8 months in the physician’s choice chemotherapy group.

Incidence of serious adverse events was 27% in the trastuzumab deruxtecan group and 25% in the physician’s choice chemotherapy group. Grade 3 or higher events occurred in 52% of the trastuzumab deruxtecan group and 67% of the physician’s choice chemotherapy group. Discontinuation due to adverse events occurred in 16% in the trastuzumab deruxtecan group and 18% in the physician’s choice chemotherapy group; 14 patients in the trastuzumab deruxtecan group and 5 patients in the physician’s choice chemotherapy group had an adverse event that was associated with death. Death due to pneumonitis in the trastuzumab deruxtecan group occurred in 2 patients. Drug-related interstitial lung disease or pneumonitis occurred in 45 patients who received trastuzumab deruxtecan. The majority of these events were grade 1 and grade 2. However, 3 patients had grade 5 interstitial lung disease or pneumonitis.

Conclusion: Treatment with trastuzumab deruxtecan led to a significant improvement in progression-free survival compared to physician’s choice chemotherapy in patients with HER2-low metastatic breast cancer.

Commentary

Trastuzumab deruxtecan is an antibody drug conjugate that consists of a humanized anti-HER2 monoclonal antibody linked to a topoisomerase 1 inhibitor. This antibody drug conjugate is unique compared with prior antibody drug conjugates such as trastuzumab emtansine in that it has a high drug-to-antibody ratio (~8). Furthermore, there appears to be a unique bystander effect resulting in off-target cytotoxicity to neighboring tumor cells, enhancing the efficacy of this novel therapy. Prior studies of trastuzumab deruxtecan have shown durable activity in heavily pretreated patients with metastatic HER2-positive breast cancer.¹

HER2-positive breast cancer represents approximately 20% of breast cancer cases in women.² Historically, HER2 positivity has been defined by strong HER2 expression with IHC staining (ie, score 3+) or HER2 amplification through ISH. Conversely, HER2-negative disease has historically been defined as those with IHC scores of 0 or 1+. This group represents approximately 60% of HER2-negative metastatic breast cancer patients.³ These patients have limited targeted treatment options after progressing on primary therapy. Prior data has shown that patients with low HER2 expression represent a heterogeneous population and thus, the historic categorization of HER2 status as positive or negative may in fact not adequately characterize the proportion of patients who may derive clinical benefit from HER2-directed therapies. Nevertheless, there have been no data to date that have shown improved outcomes in low HER2 expressers with anti-HER2 therapies.

The current studies add to the rapidly growing body of literature outlining the efficacy of the novel antibody drug conjugate trastuzumab deruxtecan. The implications of the data presented in these 2 studies are immediately practice changing.

In the DESTINY-Breast03 trial, Cortéz and colleagues show that trastuzumab deruxtecan therapy significantly prolongs progression-free survival compared with trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who have progressed on first-line trastuzumab and taxane-based therapy. With a hazard ratio of 0.28 for disease progression or death, the efficacy of trastuzumab deruxtecan highlighted in this trial clearly makes this the standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer. The overall survival in this trial was immature at the time of this analysis, and thus continued follow-up to validate the results noted here are warranted.

The DESTINY-Breast04 trial by Modi et al expands the cohort of patients who benefit from trastuzumab deruxtecan profoundly. This study defines a population of patients with HER2-low metastatic breast cancer who will now be eligible for HER2-directed therapies. These data show that therapy with trastuzumab deruxtecan leads to a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with chemotherapy in patients with metastatic breast cancer with low expression of HER2. This benefit was seen in both the estrogen receptor–positive cohort as well as the entire population, including pre-treated triple-negative disease. Furthermore, this study does not define a threshold of HER2 expression by IHC that predicts benefit with trastuzumab deruxtecan. Patients with an IHC score of 1+ as well as those with a score of 2+/ISH negative both benefit to a similar extent from trastuzumab deruxtecan. Interestingly, in the DAISY trial, antitumor activity was noted with trastuzumab deruxtecan even in those without any detectable HER2 expression on IHC.⁴ Given the inconsistency and potential false negatives of IHC along with heterogeneous HER2 expression, further work is needed to better identify patients with low levels of HER2 expression who may benefit from this novel antibody drug conjugate. Thus, a reliable test to quantitatively assess the level of HER2 expression is needed in order to determine more accurately which patients will benefit from trastuzumab deruxtecan.

Last, trastuzumab deruxtecan has been associated with interstitial lung disease and pneumonitis. Interstitial lung disease and pneumonitis occurred in approximately 10% of patients who received trastuzumab deruxtecan in the DESTINY-Breast03 trial and about 12% of patients in the DESTINY-Breast04 trial. Most of these events were grade 1 and grade 2. Nevertheless, clinicians must be aware of this risk and monitor patients frequently for the development of pneumonitis or interstitial lung disease.

Application for Clinical Practice and System Implementation

The results of the current studies show a longer progression-free survival with trastuzumab deruxtecan in both HER2-low expressing metastatic breast cancer and HER2-positive metastatic breast cancer following taxane and trastuzumab-based therapy. These results are clearly practice changing and represent a new standard of care in these patient populations. It is incumbent upon treating oncologists to work with our pathology colleagues to assess HER2 IHC thoroughly in order to identify all potential patients who may benefit from trastuzumab deruxtecan in the metastatic setting. The continued advancement of anti-HER2 therapy will undoubtedly have a significant impact on patient outcomes going forward.

Practice Points

• With a hazard ratio of 0.28 for disease progression or death, the efficacy of trastuzumab deruxtecan highlighted in the DESTINY-Breast03 trial clearly makes this the standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer.
• In the DESTINY-Breast04 trial, a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with chemotherapy was seen in patients with metastatic breast cancer with low expression of HER2, including both the estrogen receptor–positive cohort as well as the entire population, including those with pre-treated triple-negative disease.

­—Daniel Isaac, DO, MS

Study 1 Overview (Cortés et al)

Objective: To compare the efficacy and safety of trastuzumab deruxtecan with those of trastuzumab emtansine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and taxane.

Design: Phase 3, multicenter, open-label randomized trial conducted at 169 centers and 15 countries.

Setting and participants: Eligible patients had to have unresectable or metastatic HER2-positive breast cancer that had progressed during or after treatment with trastuzumab and a taxane or had disease that progressed within 6 months after neoadjuvant or adjuvant treatment involving trastuzumab or taxane. Patients with stable or previously treated brain metastases were eligible. Patients were not eligible for the study if they had symptomatic brain metastases, prior exposure to trastuzumab emtansine, or a history of interstitial lung disease.

Intervention: Patients were randomized in a 1-to-1 fashion to receive either trastuzumab deruxtecan 5.4 mg/kg every 3 weeks or trastuzumab emtansine 3.6 mg/kg every 3 weeks. Patients were stratified according to hormone-receptor status, prior treatment with epratuzumab, and the presence or absence of visceral disease.

Main outcome measures: The primary endpoint of the study was progression-free survival as determined by an independent central review. Secondary endpoints included overall survival, overall response, and safety.

Main results: A total of 524 patients were enrolled in the study, with 261 patients randomized to trastuzumab deruxtecan and 263 patients randomized to trastuzumab emtansine. The demographic and baseline characteristics were similar between the 2 cohorts, and 60% of patients in both groups received prior epratuzumab therapy. Stable brain metastases were present in around 20% of patients in each group, and 70% of patients in each group had visceral disease. The median duration of follow-up was 16.2 months with trastuzumab deruxtecan and 15.3 months with trastuzumab emtansine.

The median progression-free survival was not reached in the trastuzumab deruxtecan group and was 6.8 months in the trastuzumab emtansine group (95% CI, 5.6-8.2). At 12 months the percentage of patients alive without disease progression was significantly larger in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group. The hazard ratio for disease progression or death from any cause was 0.28 (95% CI, 0.22-0.37; P < .001). Subgroup analyses showed a benefit in progression-free survival with trastuzumab deruxtecan across all subgroups.

At the time of this analysis, the percentage of patients who were alive at 12 months was 94% with trastuzumab deruxtecan and 85.9% with trastuzumab emtansine. The response rates were significantly higher with trastuzumab deruxtecan compared with trastuzumab emtansine (79.7% vs 34.2%). A complete response was seen in 16% of patients in the trastuzumab deruxtecan arm, compared with 8.7% of patients in the trastuzumab emtansine group. The disease control rate (complete response, partial response, or stable disease) was higher in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group (96.6% vs 76.8%).

Serious adverse events were reported in 19% of patients in the trastuzumab deruxtecan group and 18% of patients in the trastuzumab emtansine group. Discontinuation due to adverse events was higher in the trastuzumab deruxtecan group, with 13.6% of patients discontinuing trastuzumab deruxtecan. Grade 3 or higher adverse events were seen in 52% of patients treated with trastuzumab deruxtecan and 48% of patients treated with trastuzumab emtansine. The most commonly reported adverse event with trastuzumab deruxtecan was nausea/vomiting and fatigue. These adverse events were seen more in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group. No drug-related grade 5 adverse events were reported.

In the trastuzumab deruxtecan group, 10.5% of patients receiving trastuzumab deruxtecan developed interstitial lung disease or pneumonitis. Seven patients had grade 1 events, 18 patients had grade 2 events, and 2 patients had grade 3 events. No grade 4 or 5 events were noted in either treatment group. The median time to onset of interstitial lung disease or pneumonitis in those receiving trastuzumab deruxtecan was 168 days (range, 33-507). Discontinuation of therapy due to interstitial lung disease or pneumonitis occurred in 8% of patients receiving trastuzumab deruxtecan and 1% of patients receiving trastuzumab emtansine.

Conclusion: Trastuzumab deruxtecan significantly decreases the risk of disease progression or death compared to trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who have progressed on prior trastuzumab and taxane-based therapy.

Study 2 Overview (Modi et al)

Objective: To assess the efficacy of trastuzumab deruxtecan in patients with unresectable or metastatic breast cancer with low levels of HER2 expression.

Design: This was a randomized, 2-group, open-label, phase 3 trial.

Setting and participants: The trial was designed with a planned enrollment of 480 patients with hormone receptor–positive disease and 60 patients with hormone receptor–negative disease. Patients were randomized in a 2:1 ratio. Randomization was stratified according to HER2 status (immunohistochemical [IHC] 1+ vs IHC 2+/in situ hybridization [ISH] negative), number of prior lines of therapy, and hormone-receptor status. IHC scores for HER2 expression were determined through central testing. Specimens that had HER2 IHC scores of 2+ were reflexed to ISH. Specimens were considered HER2-low-expressing if they had an IHC score of 1+ or if they had an IHC score of 2+ and were ISH negative.

Eligible patients had to have received chemotherapy for metastatic disease or had disease recurrence during or within 6 months after completing adjuvant chemotherapy. Patients with hormone receptor–positive disease must have had at least 1 line of endocrine therapy. Patients were eligible if they had stable brain metastases. Patients with interstitial lung disease were excluded.

Intervention: Patients were randomized to receive trastuzumab deruxtecan 5.4 mg/kg every 3 weeks or physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel).

Main outcome measures: The primary endpoint was progression-free survival in patients with hormone receptor–positive disease. Secondary endpoints were progression-free survival among all patients, overall survival in hormone receptor–positive patients, and overall survival in all patients. Additional secondary endpoints included objective response rates, duration of response, and efficacy in hormone receptor–negative patients.

Main results: A total of 373 patients were assigned to the trastuzumab deruxtecan group and 184 patients were assigned to the physician’s choice chemotherapy group; 88% of patients in each cohort were hormone receptor–positive. In the physician’s choice chemotherapy group, 51% received eribulin, 20% received capecitabine, 10% received nab-paclitaxel, 10% received gemcitabine, and 8% received paclitaxel. The demographic and baseline characteristics were similar between both cohorts. The median duration of follow-up was 18.4 months.

The median progression-free survival in the hormone receptor–positive cohort was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician’s choice chemotherapy group (HR, 0.51; 95% CI, 0.4-0.64). Subgroup analyses revealed a benefit across all subgroups. The median progression-free survival among patients with a HER2 IHC score of 1+ and those with a HER2 IHC score of 2+/negative ISH were identical. In patients who received a prior CDK 4/6 inhibitor, the median progression-free survival was also 10 months in the trastuzumab deruxtecan group. In those who were CDK 4/6- naïve, the progression-free survival was 11.7 months. The progression-free survival in all patients was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice chemotherapy group (HR, 0.46; 95% CI, 0.24-0.89).

The median overall survival in the hormone receptor–positive cohort was 23.9 months in the trastuzumab deruxtecan group compared with 17.5 months in the physician’s choice chemotherapy group (HR, 0.64; 95% CI, 0.48-0.86; P = .003). The median overall survival in the entire population was 23.4 months in the trastuzumab deruxtecan group vs 16.8 months in the physician’s choice chemotherapy group. In the hormone receptor–negative cohort, the median overall survival was 18.2 months in the trastuzumab deruxtecan group and 8.3 months in the physician’s choice chemotherapy group. Complete responses were seen in 3.6% in the trastuzumab deruxtecan group and 0.6% and the physician’s choice chemotherapy group. The median duration of response was 10.7 months in the trastuzumab deruxtecan group and 6.8 months in the physician’s choice chemotherapy group.

Incidence of serious adverse events was 27% in the trastuzumab deruxtecan group and 25% in the physician’s choice chemotherapy group. Grade 3 or higher events occurred in 52% of the trastuzumab deruxtecan group and 67% of the physician’s choice chemotherapy group. Discontinuation due to adverse events occurred in 16% in the trastuzumab deruxtecan group and 18% in the physician’s choice chemotherapy group; 14 patients in the trastuzumab deruxtecan group and 5 patients in the physician’s choice chemotherapy group had an adverse event that was associated with death. Death due to pneumonitis in the trastuzumab deruxtecan group occurred in 2 patients. Drug-related interstitial lung disease or pneumonitis occurred in 45 patients who received trastuzumab deruxtecan. The majority of these events were grade 1 and grade 2. However, 3 patients had grade 5 interstitial lung disease or pneumonitis.

Conclusion: Treatment with trastuzumab deruxtecan led to a significant improvement in progression-free survival compared to physician’s choice chemotherapy in patients with HER2-low metastatic breast cancer.

Commentary

Trastuzumab deruxtecan is an antibody drug conjugate that consists of a humanized anti-HER2 monoclonal antibody linked to a topoisomerase 1 inhibitor. This antibody drug conjugate is unique compared with prior antibody drug conjugates such as trastuzumab emtansine in that it has a high drug-to-antibody ratio (~8). Furthermore, there appears to be a unique bystander effect resulting in off-target cytotoxicity to neighboring tumor cells, enhancing the efficacy of this novel therapy. Prior studies of trastuzumab deruxtecan have shown durable activity in heavily pretreated patients with metastatic HER2-positive breast cancer.¹

HER2-positive breast cancer represents approximately 20% of breast cancer cases in women.² Historically, HER2 positivity has been defined by strong HER2 expression with IHC staining (ie, score 3+) or HER2 amplification through ISH. Conversely, HER2-negative disease has historically been defined as those with IHC scores of 0 or 1+. This group represents approximately 60% of HER2-negative metastatic breast cancer patients.³ These patients have limited targeted treatment options after progressing on primary therapy. Prior data has shown that patients with low HER2 expression represent a heterogeneous population and thus, the historic categorization of HER2 status as positive or negative may in fact not adequately characterize the proportion of patients who may derive clinical benefit from HER2-directed therapies. Nevertheless, there have been no data to date that have shown improved outcomes in low HER2 expressers with anti-HER2 therapies.

The current studies add to the rapidly growing body of literature outlining the efficacy of the novel antibody drug conjugate trastuzumab deruxtecan. The implications of the data presented in these 2 studies are immediately practice changing.

In the DESTINY-Breast03 trial, Cortéz and colleagues show that trastuzumab deruxtecan therapy significantly prolongs progression-free survival compared with trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who have progressed on first-line trastuzumab and taxane-based therapy. With a hazard ratio of 0.28 for disease progression or death, the efficacy of trastuzumab deruxtecan highlighted in this trial clearly makes this the standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer. The overall survival in this trial was immature at the time of this analysis, and thus continued follow-up to validate the results noted here are warranted.

The DESTINY-Breast04 trial by Modi et al expands the cohort of patients who benefit from trastuzumab deruxtecan profoundly. This study defines a population of patients with HER2-low metastatic breast cancer who will now be eligible for HER2-directed therapies. These data show that therapy with trastuzumab deruxtecan leads to a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with chemotherapy in patients with metastatic breast cancer with low expression of HER2. This benefit was seen in both the estrogen receptor–positive cohort as well as the entire population, including pre-treated triple-negative disease. Furthermore, this study does not define a threshold of HER2 expression by IHC that predicts benefit with trastuzumab deruxtecan. Patients with an IHC score of 1+ as well as those with a score of 2+/ISH negative both benefit to a similar extent from trastuzumab deruxtecan. Interestingly, in the DAISY trial, antitumor activity was noted with trastuzumab deruxtecan even in those without any detectable HER2 expression on IHC.⁴ Given the inconsistency and potential false negatives of IHC along with heterogeneous HER2 expression, further work is needed to better identify patients with low levels of HER2 expression who may benefit from this novel antibody drug conjugate. Thus, a reliable test to quantitatively assess the level of HER2 expression is needed in order to determine more accurately which patients will benefit from trastuzumab deruxtecan.

Last, trastuzumab deruxtecan has been associated with interstitial lung disease and pneumonitis. Interstitial lung disease and pneumonitis occurred in approximately 10% of patients who received trastuzumab deruxtecan in the DESTINY-Breast03 trial and about 12% of patients in the DESTINY-Breast04 trial. Most of these events were grade 1 and grade 2. Nevertheless, clinicians must be aware of this risk and monitor patients frequently for the development of pneumonitis or interstitial lung disease.

Application for Clinical Practice and System Implementation

The results of the current studies show a longer progression-free survival with trastuzumab deruxtecan in both HER2-low expressing metastatic breast cancer and HER2-positive metastatic breast cancer following taxane and trastuzumab-based therapy. These results are clearly practice changing and represent a new standard of care in these patient populations. It is incumbent upon treating oncologists to work with our pathology colleagues to assess HER2 IHC thoroughly in order to identify all potential patients who may benefit from trastuzumab deruxtecan in the metastatic setting. The continued advancement of anti-HER2 therapy will undoubtedly have a significant impact on patient outcomes going forward.

Practice Points

• With a hazard ratio of 0.28 for disease progression or death, the efficacy of trastuzumab deruxtecan highlighted in the DESTINY-Breast03 trial clearly makes this the standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer.
• In the DESTINY-Breast04 trial, a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with chemotherapy was seen in patients with metastatic breast cancer with low expression of HER2, including both the estrogen receptor–positive cohort as well as the entire population, including those with pre-treated triple-negative disease.

­—Daniel Isaac, DO, MS

Study 1 Overview (Cortés et al)

Objective: To compare the efficacy and safety of trastuzumab deruxtecan with those of trastuzumab emtansine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and taxane.

Design: Phase 3, multicenter, open-label randomized trial conducted at 169 centers and 15 countries.

Setting and participants: Eligible patients had to have unresectable or metastatic HER2-positive breast cancer that had progressed during or after treatment with trastuzumab and a taxane or had disease that progressed within 6 months after neoadjuvant or adjuvant treatment involving trastuzumab or taxane. Patients with stable or previously treated brain metastases were eligible. Patients were not eligible for the study if they had symptomatic brain metastases, prior exposure to trastuzumab emtansine, or a history of interstitial lung disease.

Intervention: Patients were randomized in a 1-to-1 fashion to receive either trastuzumab deruxtecan 5.4 mg/kg every 3 weeks or trastuzumab emtansine 3.6 mg/kg every 3 weeks. Patients were stratified according to hormone-receptor status, prior treatment with epratuzumab, and the presence or absence of visceral disease.

Main outcome measures: The primary endpoint of the study was progression-free survival as determined by an independent central review. Secondary endpoints included overall survival, overall response, and safety.

Main results: A total of 524 patients were enrolled in the study, with 261 patients randomized to trastuzumab deruxtecan and 263 patients randomized to trastuzumab emtansine. The demographic and baseline characteristics were similar between the 2 cohorts, and 60% of patients in both groups received prior epratuzumab therapy. Stable brain metastases were present in around 20% of patients in each group, and 70% of patients in each group had visceral disease. The median duration of follow-up was 16.2 months with trastuzumab deruxtecan and 15.3 months with trastuzumab emtansine.

The median progression-free survival was not reached in the trastuzumab deruxtecan group and was 6.8 months in the trastuzumab emtansine group (95% CI, 5.6-8.2). At 12 months the percentage of patients alive without disease progression was significantly larger in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group. The hazard ratio for disease progression or death from any cause was 0.28 (95% CI, 0.22-0.37; P < .001). Subgroup analyses showed a benefit in progression-free survival with trastuzumab deruxtecan across all subgroups.

At the time of this analysis, the percentage of patients who were alive at 12 months was 94% with trastuzumab deruxtecan and 85.9% with trastuzumab emtansine. The response rates were significantly higher with trastuzumab deruxtecan compared with trastuzumab emtansine (79.7% vs 34.2%). A complete response was seen in 16% of patients in the trastuzumab deruxtecan arm, compared with 8.7% of patients in the trastuzumab emtansine group. The disease control rate (complete response, partial response, or stable disease) was higher in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group (96.6% vs 76.8%).

Serious adverse events were reported in 19% of patients in the trastuzumab deruxtecan group and 18% of patients in the trastuzumab emtansine group. Discontinuation due to adverse events was higher in the trastuzumab deruxtecan group, with 13.6% of patients discontinuing trastuzumab deruxtecan. Grade 3 or higher adverse events were seen in 52% of patients treated with trastuzumab deruxtecan and 48% of patients treated with trastuzumab emtansine. The most commonly reported adverse event with trastuzumab deruxtecan was nausea/vomiting and fatigue. These adverse events were seen more in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group. No drug-related grade 5 adverse events were reported.

In the trastuzumab deruxtecan group, 10.5% of patients receiving trastuzumab deruxtecan developed interstitial lung disease or pneumonitis. Seven patients had grade 1 events, 18 patients had grade 2 events, and 2 patients had grade 3 events. No grade 4 or 5 events were noted in either treatment group. The median time to onset of interstitial lung disease or pneumonitis in those receiving trastuzumab deruxtecan was 168 days (range, 33-507). Discontinuation of therapy due to interstitial lung disease or pneumonitis occurred in 8% of patients receiving trastuzumab deruxtecan and 1% of patients receiving trastuzumab emtansine.

Conclusion: Trastuzumab deruxtecan significantly decreases the risk of disease progression or death compared to trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who have progressed on prior trastuzumab and taxane-based therapy.

Study 2 Overview (Modi et al)

Objective: To assess the efficacy of trastuzumab deruxtecan in patients with unresectable or metastatic breast cancer with low levels of HER2 expression.

Design: This was a randomized, 2-group, open-label, phase 3 trial.

Setting and participants: The trial was designed with a planned enrollment of 480 patients with hormone receptor–positive disease and 60 patients with hormone receptor–negative disease. Patients were randomized in a 2:1 ratio. Randomization was stratified according to HER2 status (immunohistochemical [IHC] 1+ vs IHC 2+/in situ hybridization [ISH] negative), number of prior lines of therapy, and hormone-receptor status. IHC scores for HER2 expression were determined through central testing. Specimens that had HER2 IHC scores of 2+ were reflexed to ISH. Specimens were considered HER2-low-expressing if they had an IHC score of 1+ or if they had an IHC score of 2+ and were ISH negative.

Eligible patients had to have received chemotherapy for metastatic disease or had disease recurrence during or within 6 months after completing adjuvant chemotherapy. Patients with hormone receptor–positive disease must have had at least 1 line of endocrine therapy. Patients were eligible if they had stable brain metastases. Patients with interstitial lung disease were excluded.

Intervention: Patients were randomized to receive trastuzumab deruxtecan 5.4 mg/kg every 3 weeks or physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel).

Main outcome measures: The primary endpoint was progression-free survival in patients with hormone receptor–positive disease. Secondary endpoints were progression-free survival among all patients, overall survival in hormone receptor–positive patients, and overall survival in all patients. Additional secondary endpoints included objective response rates, duration of response, and efficacy in hormone receptor–negative patients.

Main results: A total of 373 patients were assigned to the trastuzumab deruxtecan group and 184 patients were assigned to the physician’s choice chemotherapy group; 88% of patients in each cohort were hormone receptor–positive. In the physician’s choice chemotherapy group, 51% received eribulin, 20% received capecitabine, 10% received nab-paclitaxel, 10% received gemcitabine, and 8% received paclitaxel. The demographic and baseline characteristics were similar between both cohorts. The median duration of follow-up was 18.4 months.

The median progression-free survival in the hormone receptor–positive cohort was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician’s choice chemotherapy group (HR, 0.51; 95% CI, 0.4-0.64). Subgroup analyses revealed a benefit across all subgroups. The median progression-free survival among patients with a HER2 IHC score of 1+ and those with a HER2 IHC score of 2+/negative ISH were identical. In patients who received a prior CDK 4/6 inhibitor, the median progression-free survival was also 10 months in the trastuzumab deruxtecan group. In those who were CDK 4/6- naïve, the progression-free survival was 11.7 months. The progression-free survival in all patients was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice chemotherapy group (HR, 0.46; 95% CI, 0.24-0.89).

The median overall survival in the hormone receptor–positive cohort was 23.9 months in the trastuzumab deruxtecan group compared with 17.5 months in the physician’s choice chemotherapy group (HR, 0.64; 95% CI, 0.48-0.86; P = .003). The median overall survival in the entire population was 23.4 months in the trastuzumab deruxtecan group vs 16.8 months in the physician’s choice chemotherapy group. In the hormone receptor–negative cohort, the median overall survival was 18.2 months in the trastuzumab deruxtecan group and 8.3 months in the physician’s choice chemotherapy group. Complete responses were seen in 3.6% in the trastuzumab deruxtecan group and 0.6% and the physician’s choice chemotherapy group. The median duration of response was 10.7 months in the trastuzumab deruxtecan group and 6.8 months in the physician’s choice chemotherapy group.

Incidence of serious adverse events was 27% in the trastuzumab deruxtecan group and 25% in the physician’s choice chemotherapy group. Grade 3 or higher events occurred in 52% of the trastuzumab deruxtecan group and 67% of the physician’s choice chemotherapy group. Discontinuation due to adverse events occurred in 16% in the trastuzumab deruxtecan group and 18% in the physician’s choice chemotherapy group; 14 patients in the trastuzumab deruxtecan group and 5 patients in the physician’s choice chemotherapy group had an adverse event that was associated with death. Death due to pneumonitis in the trastuzumab deruxtecan group occurred in 2 patients. Drug-related interstitial lung disease or pneumonitis occurred in 45 patients who received trastuzumab deruxtecan. The majority of these events were grade 1 and grade 2. However, 3 patients had grade 5 interstitial lung disease or pneumonitis.

Conclusion: Treatment with trastuzumab deruxtecan led to a significant improvement in progression-free survival compared to physician’s choice chemotherapy in patients with HER2-low metastatic breast cancer.

Commentary

Trastuzumab deruxtecan is an antibody drug conjugate that consists of a humanized anti-HER2 monoclonal antibody linked to a topoisomerase 1 inhibitor. This antibody drug conjugate is unique compared with prior antibody drug conjugates such as trastuzumab emtansine in that it has a high drug-to-antibody ratio (~8). Furthermore, there appears to be a unique bystander effect resulting in off-target cytotoxicity to neighboring tumor cells, enhancing the efficacy of this novel therapy. Prior studies of trastuzumab deruxtecan have shown durable activity in heavily pretreated patients with metastatic HER2-positive breast cancer.¹

HER2-positive breast cancer represents approximately 20% of breast cancer cases in women.² Historically, HER2 positivity has been defined by strong HER2 expression with IHC staining (ie, score 3+) or HER2 amplification through ISH. Conversely, HER2-negative disease has historically been defined as those with IHC scores of 0 or 1+. This group represents approximately 60% of HER2-negative metastatic breast cancer patients.³ These patients have limited targeted treatment options after progressing on primary therapy. Prior data has shown that patients with low HER2 expression represent a heterogeneous population and thus, the historic categorization of HER2 status as positive or negative may in fact not adequately characterize the proportion of patients who may derive clinical benefit from HER2-directed therapies. Nevertheless, there have been no data to date that have shown improved outcomes in low HER2 expressers with anti-HER2 therapies.

The current studies add to the rapidly growing body of literature outlining the efficacy of the novel antibody drug conjugate trastuzumab deruxtecan. The implications of the data presented in these 2 studies are immediately practice changing.

In the DESTINY-Breast03 trial, Cortéz and colleagues show that trastuzumab deruxtecan therapy significantly prolongs progression-free survival compared with trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who have progressed on first-line trastuzumab and taxane-based therapy. With a hazard ratio of 0.28 for disease progression or death, the efficacy of trastuzumab deruxtecan highlighted in this trial clearly makes this the standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer. The overall survival in this trial was immature at the time of this analysis, and thus continued follow-up to validate the results noted here are warranted.

The DESTINY-Breast04 trial by Modi et al expands the cohort of patients who benefit from trastuzumab deruxtecan profoundly. This study defines a population of patients with HER2-low metastatic breast cancer who will now be eligible for HER2-directed therapies. These data show that therapy with trastuzumab deruxtecan leads to a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with chemotherapy in patients with metastatic breast cancer with low expression of HER2. This benefit was seen in both the estrogen receptor–positive cohort as well as the entire population, including pre-treated triple-negative disease. Furthermore, this study does not define a threshold of HER2 expression by IHC that predicts benefit with trastuzumab deruxtecan. Patients with an IHC score of 1+ as well as those with a score of 2+/ISH negative both benefit to a similar extent from trastuzumab deruxtecan. Interestingly, in the DAISY trial, antitumor activity was noted with trastuzumab deruxtecan even in those without any detectable HER2 expression on IHC.⁴ Given the inconsistency and potential false negatives of IHC along with heterogeneous HER2 expression, further work is needed to better identify patients with low levels of HER2 expression who may benefit from this novel antibody drug conjugate. Thus, a reliable test to quantitatively assess the level of HER2 expression is needed in order to determine more accurately which patients will benefit from trastuzumab deruxtecan.

Last, trastuzumab deruxtecan has been associated with interstitial lung disease and pneumonitis. Interstitial lung disease and pneumonitis occurred in approximately 10% of patients who received trastuzumab deruxtecan in the DESTINY-Breast03 trial and about 12% of patients in the DESTINY-Breast04 trial. Most of these events were grade 1 and grade 2. Nevertheless, clinicians must be aware of this risk and monitor patients frequently for the development of pneumonitis or interstitial lung disease.

Application for Clinical Practice and System Implementation

The results of the current studies show a longer progression-free survival with trastuzumab deruxtecan in both HER2-low expressing metastatic breast cancer and HER2-positive metastatic breast cancer following taxane and trastuzumab-based therapy. These results are clearly practice changing and represent a new standard of care in these patient populations. It is incumbent upon treating oncologists to work with our pathology colleagues to assess HER2 IHC thoroughly in order to identify all potential patients who may benefit from trastuzumab deruxtecan in the metastatic setting. The continued advancement of anti-HER2 therapy will undoubtedly have a significant impact on patient outcomes going forward.

Practice Points

• With a hazard ratio of 0.28 for disease progression or death, the efficacy of trastuzumab deruxtecan highlighted in the DESTINY-Breast03 trial clearly makes this the standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer.
• In the DESTINY-Breast04 trial, a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with chemotherapy was seen in patients with metastatic breast cancer with low expression of HER2, including both the estrogen receptor–positive cohort as well as the entire population, including those with pre-treated triple-negative disease.

­—Daniel Isaac, DO, MS

Midlife women who are of normal weight or are overweight should routinely receive counseling aimed at limiting weight gain and preventing obesity and its associated health risks, a new clinical guideline states.

The recommendation, issued by the Women’s Preventive Services Initiative (WPSI) of the American College of Obstetricians and Gynecologists (ACOG), supports regular lifestyle counseling for women aged 40-60 years with normal or overweight body mass index of 18.5-29.9 kg/m². Counseling could include individualized discussion of healthy eating and physical activity initiated by health professionals involved in preventive care.

Published online in Annals of Internal Medicine, the guideline addresses the prevalence and health burdens of obesity in U.S. women of middle age and seeks to reduce the known harms of obesity with an intervention of minimal anticipated harms. High BMI increases the risk for many chronic conditions including hypertension, dyslipidemia, type 2 diabetes, coronary artery disease, stroke, and all-cause mortality.

The best way to counsel, however, remains unclear. “Although the optimal approach could not be discerned from existing trials, a range of interventions of varying duration, frequency, and intensity showed benefit with potential clinical significance,” wrote the WPSI guideline panel, led by David P. Chelmow, MD, chair of the department of obstetrics and gynecology at Virginia Commonwealth University in Richmond.

The guideline rests on a systematic literature review led by family doctor Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center, at Oregon Health & Science University in Portland, suggesting moderate reductions in weight could be achieved by offering advice to this age group.

The federally supported WPSI was launched by ACOG in 2016. The guideline fills a gap in current recommendations in that it targets a specific risk group and specifies individual counseling based on its effectiveness and applicability in primary care settings.

In another benefit of routine counseling, the panel stated, “Normalizing counseling about healthy diet and physical activity by providing it to all midlife women may also mitigate concerns about weight stigma resulting from only counseling women with obesity.”

The panelists noted that during 2017-2018, the prevalence of obesity (BMI ≥ 30.0 kg/m²) was 43.3% among U.S. women aged 40-59 years, while the prevalence of severe obesity (BMI ≥ 40.0 kg/m²) was highest in this age group at 11.5%. “Midlife women gain weight at an average of approximately 1.5 pounds per year, which increases their risk for transitioning from normal or overweight to obese BMI,” the panelists wrote.

The review

Dr. Cantor’s group analyzed seven randomized controlled trials (RCTs) published up to October 2021 from 12 publications involving 51,638 participants. Although the trials were largely small and heterogeneous, they suggested that counseling may result in modest differences in weight change without causing important harms.

Four RCTs showed significant favorable weight changes for counseling over no-counseling control groups, with a mean difference of 0.87 to 2.5 kg, whereas one trial of counseling and two trials of exercise showed no differences. One of two RCTs reported improved quality-of-life measures.

As for harms, while interventions did not increase measures of depression or stress in one trial, self-reported falls (37% vs. 29%, P < .001) and injuries (19% vs. 14%, P = .03) were more frequent with exercise counseling in one trial.

“More research is needed to determine optimal content, frequency, length, and number of sessions required and should include additional patient populations,” Dr. Cantor and associates wrote.

In terms of limitations, the authors acknowledged that trials of behavioral interventions in maintaining or reducing weight in midlife women demonstrate small magnitudes of effect.

Offering a nonparticipant’s perspective on the WPSI guideline for this news organization, JoAnn E. Manson, MD, DrPH, MACP, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, said its message is of prime importance for women of middle age and it goes beyond concern about pounds lost or gained.

“Midlife and the transition to menopause are high-risk periods for women in terms of typical changes in body composition that increase the risk of adverse cardiometabolic outcomes,” said Dr. Manson, professor of women’s health at Harvard Medical School, Boston. “Counseling women should be a priority for physicians in clinical practice. And it’s not just whether weight gain is reflected on the scales or not but whether there’s an increase in central abdominal fat, a decrease in lean muscle mass, and an increase in adverse glucose tolerance.”

It is essential for women to be vigilant at this time, she added, and their exercise regimens should include strength and resistance training to preserve lean muscle mass and boost metabolic rate. Dr. Manson’s group has issued several statements stressing how important it is for clinicians to take decisive action on the counseling front and how they can do this in very little time during routine practice.

Also in full support of the guideline is Mary L. Rosser, MD, PhD, assistant professor of women’s health in obstetrics and gynecology at Columbia University Irving Medical Center in New York. “Midlife is a wonderful opportunity to encourage patients to assess their overall health status and make changes to impact their future health. Women in middle age tend to experience weight gain due to a variety of factors including aging and lifestyle,” said Dr. Rosser, who was not involved in the writing of the review or guideline.

While aging and genetics cannot be altered, behaviors can, and in her view, favorable behaviors would also include stress reduction and adequate sleep.

“The importance of reducing obesity with early intervention and prevention must focus on all women,” Dr. Rosser said. “We must narrow the inequities gap in care especially for high-risk minority groups and underserved populations. This will reduce disease and death and provide women the gift of active living and feeling better.”

The WPSI authors have made available a summary of the review and guideline for patients.

The systematic review and clinical guideline were funded by the federal Health Resources and Services Administration through ACOG. The authors of the guideline and the review authors disclosed no relevant financial conflicts of interest. Dr. Manson and Dr. Rosser disclosed no relevant competing interests with regard to their comments.

Midlife women who are of normal weight or are overweight should routinely receive counseling aimed at limiting weight gain and preventing obesity and its associated health risks, a new clinical guideline states.

The recommendation, issued by the Women’s Preventive Services Initiative (WPSI) of the American College of Obstetricians and Gynecologists (ACOG), supports regular lifestyle counseling for women aged 40-60 years with normal or overweight body mass index of 18.5-29.9 kg/m². Counseling could include individualized discussion of healthy eating and physical activity initiated by health professionals involved in preventive care.

Published online in Annals of Internal Medicine, the guideline addresses the prevalence and health burdens of obesity in U.S. women of middle age and seeks to reduce the known harms of obesity with an intervention of minimal anticipated harms. High BMI increases the risk for many chronic conditions including hypertension, dyslipidemia, type 2 diabetes, coronary artery disease, stroke, and all-cause mortality.

The best way to counsel, however, remains unclear. “Although the optimal approach could not be discerned from existing trials, a range of interventions of varying duration, frequency, and intensity showed benefit with potential clinical significance,” wrote the WPSI guideline panel, led by David P. Chelmow, MD, chair of the department of obstetrics and gynecology at Virginia Commonwealth University in Richmond.

The guideline rests on a systematic literature review led by family doctor Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center, at Oregon Health & Science University in Portland, suggesting moderate reductions in weight could be achieved by offering advice to this age group.

The federally supported WPSI was launched by ACOG in 2016. The guideline fills a gap in current recommendations in that it targets a specific risk group and specifies individual counseling based on its effectiveness and applicability in primary care settings.

In another benefit of routine counseling, the panel stated, “Normalizing counseling about healthy diet and physical activity by providing it to all midlife women may also mitigate concerns about weight stigma resulting from only counseling women with obesity.”

The panelists noted that during 2017-2018, the prevalence of obesity (BMI ≥ 30.0 kg/m²) was 43.3% among U.S. women aged 40-59 years, while the prevalence of severe obesity (BMI ≥ 40.0 kg/m²) was highest in this age group at 11.5%. “Midlife women gain weight at an average of approximately 1.5 pounds per year, which increases their risk for transitioning from normal or overweight to obese BMI,” the panelists wrote.

The review

Dr. Cantor’s group analyzed seven randomized controlled trials (RCTs) published up to October 2021 from 12 publications involving 51,638 participants. Although the trials were largely small and heterogeneous, they suggested that counseling may result in modest differences in weight change without causing important harms.

Four RCTs showed significant favorable weight changes for counseling over no-counseling control groups, with a mean difference of 0.87 to 2.5 kg, whereas one trial of counseling and two trials of exercise showed no differences. One of two RCTs reported improved quality-of-life measures.

As for harms, while interventions did not increase measures of depression or stress in one trial, self-reported falls (37% vs. 29%, P < .001) and injuries (19% vs. 14%, P = .03) were more frequent with exercise counseling in one trial.

“More research is needed to determine optimal content, frequency, length, and number of sessions required and should include additional patient populations,” Dr. Cantor and associates wrote.

In terms of limitations, the authors acknowledged that trials of behavioral interventions in maintaining or reducing weight in midlife women demonstrate small magnitudes of effect.

Offering a nonparticipant’s perspective on the WPSI guideline for this news organization, JoAnn E. Manson, MD, DrPH, MACP, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, said its message is of prime importance for women of middle age and it goes beyond concern about pounds lost or gained.

“Midlife and the transition to menopause are high-risk periods for women in terms of typical changes in body composition that increase the risk of adverse cardiometabolic outcomes,” said Dr. Manson, professor of women’s health at Harvard Medical School, Boston. “Counseling women should be a priority for physicians in clinical practice. And it’s not just whether weight gain is reflected on the scales or not but whether there’s an increase in central abdominal fat, a decrease in lean muscle mass, and an increase in adverse glucose tolerance.”

It is essential for women to be vigilant at this time, she added, and their exercise regimens should include strength and resistance training to preserve lean muscle mass and boost metabolic rate. Dr. Manson’s group has issued several statements stressing how important it is for clinicians to take decisive action on the counseling front and how they can do this in very little time during routine practice.

Also in full support of the guideline is Mary L. Rosser, MD, PhD, assistant professor of women’s health in obstetrics and gynecology at Columbia University Irving Medical Center in New York. “Midlife is a wonderful opportunity to encourage patients to assess their overall health status and make changes to impact their future health. Women in middle age tend to experience weight gain due to a variety of factors including aging and lifestyle,” said Dr. Rosser, who was not involved in the writing of the review or guideline.

While aging and genetics cannot be altered, behaviors can, and in her view, favorable behaviors would also include stress reduction and adequate sleep.

“The importance of reducing obesity with early intervention and prevention must focus on all women,” Dr. Rosser said. “We must narrow the inequities gap in care especially for high-risk minority groups and underserved populations. This will reduce disease and death and provide women the gift of active living and feeling better.”

The WPSI authors have made available a summary of the review and guideline for patients.

The systematic review and clinical guideline were funded by the federal Health Resources and Services Administration through ACOG. The authors of the guideline and the review authors disclosed no relevant financial conflicts of interest. Dr. Manson and Dr. Rosser disclosed no relevant competing interests with regard to their comments.

Midlife women who are of normal weight or are overweight should routinely receive counseling aimed at limiting weight gain and preventing obesity and its associated health risks, a new clinical guideline states.

The recommendation, issued by the Women’s Preventive Services Initiative (WPSI) of the American College of Obstetricians and Gynecologists (ACOG), supports regular lifestyle counseling for women aged 40-60 years with normal or overweight body mass index of 18.5-29.9 kg/m². Counseling could include individualized discussion of healthy eating and physical activity initiated by health professionals involved in preventive care.

Published online in Annals of Internal Medicine, the guideline addresses the prevalence and health burdens of obesity in U.S. women of middle age and seeks to reduce the known harms of obesity with an intervention of minimal anticipated harms. High BMI increases the risk for many chronic conditions including hypertension, dyslipidemia, type 2 diabetes, coronary artery disease, stroke, and all-cause mortality.

The best way to counsel, however, remains unclear. “Although the optimal approach could not be discerned from existing trials, a range of interventions of varying duration, frequency, and intensity showed benefit with potential clinical significance,” wrote the WPSI guideline panel, led by David P. Chelmow, MD, chair of the department of obstetrics and gynecology at Virginia Commonwealth University in Richmond.

The guideline rests on a systematic literature review led by family doctor Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center, at Oregon Health & Science University in Portland, suggesting moderate reductions in weight could be achieved by offering advice to this age group.

The federally supported WPSI was launched by ACOG in 2016. The guideline fills a gap in current recommendations in that it targets a specific risk group and specifies individual counseling based on its effectiveness and applicability in primary care settings.

In another benefit of routine counseling, the panel stated, “Normalizing counseling about healthy diet and physical activity by providing it to all midlife women may also mitigate concerns about weight stigma resulting from only counseling women with obesity.”

The panelists noted that during 2017-2018, the prevalence of obesity (BMI ≥ 30.0 kg/m²) was 43.3% among U.S. women aged 40-59 years, while the prevalence of severe obesity (BMI ≥ 40.0 kg/m²) was highest in this age group at 11.5%. “Midlife women gain weight at an average of approximately 1.5 pounds per year, which increases their risk for transitioning from normal or overweight to obese BMI,” the panelists wrote.

The review

Dr. Cantor’s group analyzed seven randomized controlled trials (RCTs) published up to October 2021 from 12 publications involving 51,638 participants. Although the trials were largely small and heterogeneous, they suggested that counseling may result in modest differences in weight change without causing important harms.

Four RCTs showed significant favorable weight changes for counseling over no-counseling control groups, with a mean difference of 0.87 to 2.5 kg, whereas one trial of counseling and two trials of exercise showed no differences. One of two RCTs reported improved quality-of-life measures.

As for harms, while interventions did not increase measures of depression or stress in one trial, self-reported falls (37% vs. 29%, P < .001) and injuries (19% vs. 14%, P = .03) were more frequent with exercise counseling in one trial.

“More research is needed to determine optimal content, frequency, length, and number of sessions required and should include additional patient populations,” Dr. Cantor and associates wrote.

In terms of limitations, the authors acknowledged that trials of behavioral interventions in maintaining or reducing weight in midlife women demonstrate small magnitudes of effect.

Offering a nonparticipant’s perspective on the WPSI guideline for this news organization, JoAnn E. Manson, MD, DrPH, MACP, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, said its message is of prime importance for women of middle age and it goes beyond concern about pounds lost or gained.

“Midlife and the transition to menopause are high-risk periods for women in terms of typical changes in body composition that increase the risk of adverse cardiometabolic outcomes,” said Dr. Manson, professor of women’s health at Harvard Medical School, Boston. “Counseling women should be a priority for physicians in clinical practice. And it’s not just whether weight gain is reflected on the scales or not but whether there’s an increase in central abdominal fat, a decrease in lean muscle mass, and an increase in adverse glucose tolerance.”

It is essential for women to be vigilant at this time, she added, and their exercise regimens should include strength and resistance training to preserve lean muscle mass and boost metabolic rate. Dr. Manson’s group has issued several statements stressing how important it is for clinicians to take decisive action on the counseling front and how they can do this in very little time during routine practice.

Also in full support of the guideline is Mary L. Rosser, MD, PhD, assistant professor of women’s health in obstetrics and gynecology at Columbia University Irving Medical Center in New York. “Midlife is a wonderful opportunity to encourage patients to assess their overall health status and make changes to impact their future health. Women in middle age tend to experience weight gain due to a variety of factors including aging and lifestyle,” said Dr. Rosser, who was not involved in the writing of the review or guideline.

While aging and genetics cannot be altered, behaviors can, and in her view, favorable behaviors would also include stress reduction and adequate sleep.

“The importance of reducing obesity with early intervention and prevention must focus on all women,” Dr. Rosser said. “We must narrow the inequities gap in care especially for high-risk minority groups and underserved populations. This will reduce disease and death and provide women the gift of active living and feeling better.”

The WPSI authors have made available a summary of the review and guideline for patients.

The systematic review and clinical guideline were funded by the federal Health Resources and Services Administration through ACOG. The authors of the guideline and the review authors disclosed no relevant financial conflicts of interest. Dr. Manson and Dr. Rosser disclosed no relevant competing interests with regard to their comments.

The names of the doctors in this story have been changed at their request because of fear of legal repercussions and/or professional retaliation.

When an Ohio ob.gyn. had a patient in need of an abortion in July 2022, he knew he had to move quickly.

Daniel, who also sees patients at an abortion clinic, was treating a woman who came in for an abortion around 5 weeks into her pregnancy. And after going through the mandatory waiting periods, the required ultrasounds at each appointment, the consent process, and the options counseling, she was set for a surgical abortion the following Monday.

But on Monday, pre-op tests showed that her blood pressure was very high, posing a serious health risk if Daniel proceeded with the surgery.

Before the Supreme Court overturned Roe v. Wade in June, Daniel would have sent the patient home with instructions on how to lower her blood pressure over time. But the patient now had just four days to show the necessary improvement.

In this case, everything worked out. The patient returned Thursday and was able to have the procedure. But this is just one of the many day-to-day medical decisions abortion providers are now having to make with the changing legal risks being as top-of-mind to doctors as the safety of their patients.

Daniel said he doesn’t want the Ohio abortion law to change the way he communicates with his patients. As far as he knows, it’s still legal to talk to patients about self-managed abortions, as long as everything is unbiased and clearly stated, he says.

“But I don’t think I would get a lot of institutional support to have those conversations with patients because of the perceived legal liability,” says Daniel. “I will still have those conversations, but I’m not going to tell my employer that I’m having them and I’m not going to document them in the chart.”

Daniel is aware that having these kinds of discussions, or entertaining the possibility of omitting certain information from patient records, runs the risk of legal and professional consequences. Enforcement of these rules is foggy, too.

Under the Ohio law, if a fellow staff member suspects you of violating a law, you could be reported to a supervisor or licensing body. Abortion providers are aware they must be cautious about what they say because anti-abortion activitists, posing as patients, have secretly recorded conversations in the past, Daniel says.
 

Enforcement: The past, present, and future legal risks

Before Roe, enforcement of illegal abortion was spotty, says Mary Ziegler, JD, a professor at Florida State University College of Law, who specializes in the legal history of reproductive rights. At the start of the late 19th century, the doctors who provided illegal abortions would, in most cases, be prosecuted if a patient died as a result of the procedure.

A doctor in Ashland, Pa., named Robert Spencer was known for providing abortions in the small mining town where he practiced in the 1920s. He was reportedly arrested three times – once after a patient died as a result of abortion complications – but was ultimately acquitted.

For many doctors performing abortions at the time, “it was very much a kind of roll of the dice,” Ms. Ziegler says. “There was a sense that these laws were not enforced very much.”

Carole Joffe, PhD, a sociologist with expertise in reproductive health, recalls that there were very few doctors arrested, given the sheer number of abortions that were performed. The American College of Obstetricians and Gynecologists estimates that, in the years leading up to the original Roe decision, about 1.2 million women in the U.S. had illegal abortions – a number that exceeds today’s estimates.

Among the most notable cases of a doctor being detained was the arrest of gynecologist Jane Hodgson, MD, in 1970. Dr. Hodgson intentionally violated Minnesota law, which prohibited all abortions except in cases that were life-threatening to the patient.

After performing an abortion on a patient who had contracted rubella, also known as German measles, Dr. Hodgson was arrested, sentenced to 30 days in jail, and put on a year-long probation. She did not end up serving any time in jail, and her conviction was overturned after the Roe decision in 1973.

Now, the abortion restrictions being passed in many states have authorized much more sweeping penalties than those that existed in the pre-Roe era. According to Joffe, there is one key reason why we can anticipate more doctor arrests now.

“There simply was not the modern anti-abortion movement that we have come to know,” she says. “In the old days, there was not that much legal surveillance, and things were very unsafe. Fast forward to the present, we have much safer options now – like medication abortion pills – but we have a very different legal environment.”

Carmel Shachar, JD, MPH, a law and health policy expert at Harvard Law School, also expects that we will see more frequent prosecutions of doctors who provide abortion.

“There’s so much more data available through medical record-keeping and information generated by our phones and internet searches, that I think it would be much harder for a physician to fly under the radar,” Ms. Shachar says.

Also, Ms. Shachar emphasizes the power of prosecutorial discretion in abortion cases, where one prosecutor may choose to apply a law much more aggressively than another prosecutor in the next county over. Such has been seen in DeKalb County, Ga., which includes parts of Atlanta, where District Attorney Sherry Boston says she plans to use her prosecutorial discretion to address crimes like rape and murder, rather than “potentially investigat[ing] women and doctors for medical decisions,” Bloomberg Law reported. State Sen. Jen Jordan, the Democratic nominee for Georgia attorney general, has also said that, if elected, she would not enforce the state’s new 6-week abortion ban.
 

Is there a legal path forward for abortion care in states that forbid it?

Robin, an ob.gyn., became a complex family planning fellow in Utah to seek out further medical training and education in abortion care. Her plan was to solidify this as an area of expertise, so that, upon completing her fellowship, she could move back to her home state of Arizona to provide services there.

In Utah, where she currently practices, abortion is banned after 18 weeks. In Arizona, abortion is still allowed up to 24-26 weeks, until a pregnancy reaches “viability” (when a fetus is developed enough that it is able to survive outside the uterus with medical assistance). But new restrictions in Arizona may go into effect as early as September which would prohibit abortions after 15 weeks.

Despite the uncertain future of abortion access in Arizona, Robin still plans on moving there after her fellowship, but she hopes to travel to surrounding states to help provide abortion care where it’s less restricted. Even if she isn’t able to provide abortions at all, she says that there are still ways to help patients get safe, above-board abortions so as not to repeat the dangerous and often gruesome outcomes of self-induced abortions or those done by illegitimate practitioners before Roe.

“One of the roles that I think I can have as a physician is helping people with wraparound care for self-managed abortion,” says Robin. “If they can get the [abortion] pills online, then I can do the ultrasound beforehand, I can do the ultrasound after, I can talk them through it. I can help them with all the aspects of this care, I just can’t give them the pills myself.”

Whether a doctor can be penalized for “aiding and abetting” abortions that happen in different states remains an open question. In Texas, for example, Senate Bill 8 – which took effect Sept. 1, 2021 – not only established a fetal heartbeat law but added language that would allow private citizens to sue anyone who “knowingly engages in conduct that aids or abets the performance or inducement of an abortion” or anyone who even intends to do so.

That’s what happened to Alan Braid, MD, an ob.gyn. based in San Antonio. He confessed in a Washington Post op-ed that he had performed an abortion after cardiac activity had been detected in the pregnancy. Aware of the legal risks, he has since been sued by three people, and those cases are still underway.

But Ms. Ziegler says the chances of a doctor from a progressive state actually getting extradited and prosecuted by a state with restrictive abortion laws is pretty low – not zero, but low.

Like Robin, Natalie – an ob.gyn. in her early 30s – is a complex family planning fellow in Massachusetts. After her fellowship, she wants to return to Texas, where she completed her residency training.

“I’m at the point in my training where everyone starts looking for jobs and figuring out their next steps,” says Natalie. “The Dobbs decision introduced a ton of chaos due to the vagueness in the laws and how they get enforced, and then there’s chaos within institutions themselves and what kind of risk tolerance they have.”

Looking towards her future career path, Natalie says that she would not consider a job at an institution that didn’t allow her to teach abortion care to students, speak publicly about abortion rights, or let her travel outside of Texas to continue providing abortion care. She’s also preemptively seeking legal counsel and general guidance – advice that Ms. Ziegler strongly urges doctors to heed, sooner rather than later.

In states that have strict abortion bans with exceptions for life-threatening cases, there is still a lack of clarity around what is actually considered life-threatening enough to pass as an exception.

“Is it life-threatening in the next 6 hours? 24 hours? Seven days? One month?” Robin asks. “In medicine, we don’t necessarily talk about if something is life-threatening or not, we just say that there’s a high risk of X thing happening in X period of time. What’s the threshold at which that meets legal criteria? Nobody has an answer for that.”

Robin explains that, in her patients who have cancer, a pregnancy wouldn’t “necessarily kill them within the span of the next 9 months, but it could certainly accelerate their disease that could kill them within the next year or two.”

Right now, she says she doesn’t know what she would do if and when she is put in that position as a doctor.

“I didn’t go to medical school and become a doctor to become a felon,” says Robin. “Our goal is to make as many legal changes as we can to protect our patients and then practice as much harm reduction and as much care as we can within the letter of the law.”

A version of this article first appeared on WebMD.com.

The names of the doctors in this story have been changed at their request because of fear of legal repercussions and/or professional retaliation.

When an Ohio ob.gyn. had a patient in need of an abortion in July 2022, he knew he had to move quickly.

Daniel, who also sees patients at an abortion clinic, was treating a woman who came in for an abortion around 5 weeks into her pregnancy. And after going through the mandatory waiting periods, the required ultrasounds at each appointment, the consent process, and the options counseling, she was set for a surgical abortion the following Monday.

But on Monday, pre-op tests showed that her blood pressure was very high, posing a serious health risk if Daniel proceeded with the surgery.

Before the Supreme Court overturned Roe v. Wade in June, Daniel would have sent the patient home with instructions on how to lower her blood pressure over time. But the patient now had just four days to show the necessary improvement.

In this case, everything worked out. The patient returned Thursday and was able to have the procedure. But this is just one of the many day-to-day medical decisions abortion providers are now having to make with the changing legal risks being as top-of-mind to doctors as the safety of their patients.

Daniel said he doesn’t want the Ohio abortion law to change the way he communicates with his patients. As far as he knows, it’s still legal to talk to patients about self-managed abortions, as long as everything is unbiased and clearly stated, he says.

“But I don’t think I would get a lot of institutional support to have those conversations with patients because of the perceived legal liability,” says Daniel. “I will still have those conversations, but I’m not going to tell my employer that I’m having them and I’m not going to document them in the chart.”

Daniel is aware that having these kinds of discussions, or entertaining the possibility of omitting certain information from patient records, runs the risk of legal and professional consequences. Enforcement of these rules is foggy, too.

Under the Ohio law, if a fellow staff member suspects you of violating a law, you could be reported to a supervisor or licensing body. Abortion providers are aware they must be cautious about what they say because anti-abortion activitists, posing as patients, have secretly recorded conversations in the past, Daniel says.
 

Enforcement: The past, present, and future legal risks

Before Roe, enforcement of illegal abortion was spotty, says Mary Ziegler, JD, a professor at Florida State University College of Law, who specializes in the legal history of reproductive rights. At the start of the late 19th century, the doctors who provided illegal abortions would, in most cases, be prosecuted if a patient died as a result of the procedure.

A doctor in Ashland, Pa., named Robert Spencer was known for providing abortions in the small mining town where he practiced in the 1920s. He was reportedly arrested three times – once after a patient died as a result of abortion complications – but was ultimately acquitted.

For many doctors performing abortions at the time, “it was very much a kind of roll of the dice,” Ms. Ziegler says. “There was a sense that these laws were not enforced very much.”

Carole Joffe, PhD, a sociologist with expertise in reproductive health, recalls that there were very few doctors arrested, given the sheer number of abortions that were performed. The American College of Obstetricians and Gynecologists estimates that, in the years leading up to the original Roe decision, about 1.2 million women in the U.S. had illegal abortions – a number that exceeds today’s estimates.

Among the most notable cases of a doctor being detained was the arrest of gynecologist Jane Hodgson, MD, in 1970. Dr. Hodgson intentionally violated Minnesota law, which prohibited all abortions except in cases that were life-threatening to the patient.

After performing an abortion on a patient who had contracted rubella, also known as German measles, Dr. Hodgson was arrested, sentenced to 30 days in jail, and put on a year-long probation. She did not end up serving any time in jail, and her conviction was overturned after the Roe decision in 1973.

Now, the abortion restrictions being passed in many states have authorized much more sweeping penalties than those that existed in the pre-Roe era. According to Joffe, there is one key reason why we can anticipate more doctor arrests now.

“There simply was not the modern anti-abortion movement that we have come to know,” she says. “In the old days, there was not that much legal surveillance, and things were very unsafe. Fast forward to the present, we have much safer options now – like medication abortion pills – but we have a very different legal environment.”

Carmel Shachar, JD, MPH, a law and health policy expert at Harvard Law School, also expects that we will see more frequent prosecutions of doctors who provide abortion.

“There’s so much more data available through medical record-keeping and information generated by our phones and internet searches, that I think it would be much harder for a physician to fly under the radar,” Ms. Shachar says.

Also, Ms. Shachar emphasizes the power of prosecutorial discretion in abortion cases, where one prosecutor may choose to apply a law much more aggressively than another prosecutor in the next county over. Such has been seen in DeKalb County, Ga., which includes parts of Atlanta, where District Attorney Sherry Boston says she plans to use her prosecutorial discretion to address crimes like rape and murder, rather than “potentially investigat[ing] women and doctors for medical decisions,” Bloomberg Law reported. State Sen. Jen Jordan, the Democratic nominee for Georgia attorney general, has also said that, if elected, she would not enforce the state’s new 6-week abortion ban.
 

Is there a legal path forward for abortion care in states that forbid it?

Robin, an ob.gyn., became a complex family planning fellow in Utah to seek out further medical training and education in abortion care. Her plan was to solidify this as an area of expertise, so that, upon completing her fellowship, she could move back to her home state of Arizona to provide services there.

In Utah, where she currently practices, abortion is banned after 18 weeks. In Arizona, abortion is still allowed up to 24-26 weeks, until a pregnancy reaches “viability” (when a fetus is developed enough that it is able to survive outside the uterus with medical assistance). But new restrictions in Arizona may go into effect as early as September which would prohibit abortions after 15 weeks.

Despite the uncertain future of abortion access in Arizona, Robin still plans on moving there after her fellowship, but she hopes to travel to surrounding states to help provide abortion care where it’s less restricted. Even if she isn’t able to provide abortions at all, she says that there are still ways to help patients get safe, above-board abortions so as not to repeat the dangerous and often gruesome outcomes of self-induced abortions or those done by illegitimate practitioners before Roe.

“One of the roles that I think I can have as a physician is helping people with wraparound care for self-managed abortion,” says Robin. “If they can get the [abortion] pills online, then I can do the ultrasound beforehand, I can do the ultrasound after, I can talk them through it. I can help them with all the aspects of this care, I just can’t give them the pills myself.”

Whether a doctor can be penalized for “aiding and abetting” abortions that happen in different states remains an open question. In Texas, for example, Senate Bill 8 – which took effect Sept. 1, 2021 – not only established a fetal heartbeat law but added language that would allow private citizens to sue anyone who “knowingly engages in conduct that aids or abets the performance or inducement of an abortion” or anyone who even intends to do so.

That’s what happened to Alan Braid, MD, an ob.gyn. based in San Antonio. He confessed in a Washington Post op-ed that he had performed an abortion after cardiac activity had been detected in the pregnancy. Aware of the legal risks, he has since been sued by three people, and those cases are still underway.

But Ms. Ziegler says the chances of a doctor from a progressive state actually getting extradited and prosecuted by a state with restrictive abortion laws is pretty low – not zero, but low.

Like Robin, Natalie – an ob.gyn. in her early 30s – is a complex family planning fellow in Massachusetts. After her fellowship, she wants to return to Texas, where she completed her residency training.

“I’m at the point in my training where everyone starts looking for jobs and figuring out their next steps,” says Natalie. “The Dobbs decision introduced a ton of chaos due to the vagueness in the laws and how they get enforced, and then there’s chaos within institutions themselves and what kind of risk tolerance they have.”

Looking towards her future career path, Natalie says that she would not consider a job at an institution that didn’t allow her to teach abortion care to students, speak publicly about abortion rights, or let her travel outside of Texas to continue providing abortion care. She’s also preemptively seeking legal counsel and general guidance – advice that Ms. Ziegler strongly urges doctors to heed, sooner rather than later.

In states that have strict abortion bans with exceptions for life-threatening cases, there is still a lack of clarity around what is actually considered life-threatening enough to pass as an exception.

“Is it life-threatening in the next 6 hours? 24 hours? Seven days? One month?” Robin asks. “In medicine, we don’t necessarily talk about if something is life-threatening or not, we just say that there’s a high risk of X thing happening in X period of time. What’s the threshold at which that meets legal criteria? Nobody has an answer for that.”

Robin explains that, in her patients who have cancer, a pregnancy wouldn’t “necessarily kill them within the span of the next 9 months, but it could certainly accelerate their disease that could kill them within the next year or two.”

Right now, she says she doesn’t know what she would do if and when she is put in that position as a doctor.

“I didn’t go to medical school and become a doctor to become a felon,” says Robin. “Our goal is to make as many legal changes as we can to protect our patients and then practice as much harm reduction and as much care as we can within the letter of the law.”

A version of this article first appeared on WebMD.com.

The names of the doctors in this story have been changed at their request because of fear of legal repercussions and/or professional retaliation.

When an Ohio ob.gyn. had a patient in need of an abortion in July 2022, he knew he had to move quickly.

Daniel, who also sees patients at an abortion clinic, was treating a woman who came in for an abortion around 5 weeks into her pregnancy. And after going through the mandatory waiting periods, the required ultrasounds at each appointment, the consent process, and the options counseling, she was set for a surgical abortion the following Monday.

But on Monday, pre-op tests showed that her blood pressure was very high, posing a serious health risk if Daniel proceeded with the surgery.

Before the Supreme Court overturned Roe v. Wade in June, Daniel would have sent the patient home with instructions on how to lower her blood pressure over time. But the patient now had just four days to show the necessary improvement.

In this case, everything worked out. The patient returned Thursday and was able to have the procedure. But this is just one of the many day-to-day medical decisions abortion providers are now having to make with the changing legal risks being as top-of-mind to doctors as the safety of their patients.

Daniel said he doesn’t want the Ohio abortion law to change the way he communicates with his patients. As far as he knows, it’s still legal to talk to patients about self-managed abortions, as long as everything is unbiased and clearly stated, he says.

“But I don’t think I would get a lot of institutional support to have those conversations with patients because of the perceived legal liability,” says Daniel. “I will still have those conversations, but I’m not going to tell my employer that I’m having them and I’m not going to document them in the chart.”

Daniel is aware that having these kinds of discussions, or entertaining the possibility of omitting certain information from patient records, runs the risk of legal and professional consequences. Enforcement of these rules is foggy, too.

Under the Ohio law, if a fellow staff member suspects you of violating a law, you could be reported to a supervisor or licensing body. Abortion providers are aware they must be cautious about what they say because anti-abortion activitists, posing as patients, have secretly recorded conversations in the past, Daniel says.
 

Enforcement: The past, present, and future legal risks

Before Roe, enforcement of illegal abortion was spotty, says Mary Ziegler, JD, a professor at Florida State University College of Law, who specializes in the legal history of reproductive rights. At the start of the late 19th century, the doctors who provided illegal abortions would, in most cases, be prosecuted if a patient died as a result of the procedure.

A doctor in Ashland, Pa., named Robert Spencer was known for providing abortions in the small mining town where he practiced in the 1920s. He was reportedly arrested three times – once after a patient died as a result of abortion complications – but was ultimately acquitted.

For many doctors performing abortions at the time, “it was very much a kind of roll of the dice,” Ms. Ziegler says. “There was a sense that these laws were not enforced very much.”

Carole Joffe, PhD, a sociologist with expertise in reproductive health, recalls that there were very few doctors arrested, given the sheer number of abortions that were performed. The American College of Obstetricians and Gynecologists estimates that, in the years leading up to the original Roe decision, about 1.2 million women in the U.S. had illegal abortions – a number that exceeds today’s estimates.

Among the most notable cases of a doctor being detained was the arrest of gynecologist Jane Hodgson, MD, in 1970. Dr. Hodgson intentionally violated Minnesota law, which prohibited all abortions except in cases that were life-threatening to the patient.

After performing an abortion on a patient who had contracted rubella, also known as German measles, Dr. Hodgson was arrested, sentenced to 30 days in jail, and put on a year-long probation. She did not end up serving any time in jail, and her conviction was overturned after the Roe decision in 1973.

Now, the abortion restrictions being passed in many states have authorized much more sweeping penalties than those that existed in the pre-Roe era. According to Joffe, there is one key reason why we can anticipate more doctor arrests now.

“There simply was not the modern anti-abortion movement that we have come to know,” she says. “In the old days, there was not that much legal surveillance, and things were very unsafe. Fast forward to the present, we have much safer options now – like medication abortion pills – but we have a very different legal environment.”

Carmel Shachar, JD, MPH, a law and health policy expert at Harvard Law School, also expects that we will see more frequent prosecutions of doctors who provide abortion.

“There’s so much more data available through medical record-keeping and information generated by our phones and internet searches, that I think it would be much harder for a physician to fly under the radar,” Ms. Shachar says.

Also, Ms. Shachar emphasizes the power of prosecutorial discretion in abortion cases, where one prosecutor may choose to apply a law much more aggressively than another prosecutor in the next county over. Such has been seen in DeKalb County, Ga., which includes parts of Atlanta, where District Attorney Sherry Boston says she plans to use her prosecutorial discretion to address crimes like rape and murder, rather than “potentially investigat[ing] women and doctors for medical decisions,” Bloomberg Law reported. State Sen. Jen Jordan, the Democratic nominee for Georgia attorney general, has also said that, if elected, she would not enforce the state’s new 6-week abortion ban.
 

Is there a legal path forward for abortion care in states that forbid it?

Robin, an ob.gyn., became a complex family planning fellow in Utah to seek out further medical training and education in abortion care. Her plan was to solidify this as an area of expertise, so that, upon completing her fellowship, she could move back to her home state of Arizona to provide services there.

In Utah, where she currently practices, abortion is banned after 18 weeks. In Arizona, abortion is still allowed up to 24-26 weeks, until a pregnancy reaches “viability” (when a fetus is developed enough that it is able to survive outside the uterus with medical assistance). But new restrictions in Arizona may go into effect as early as September which would prohibit abortions after 15 weeks.

Despite the uncertain future of abortion access in Arizona, Robin still plans on moving there after her fellowship, but she hopes to travel to surrounding states to help provide abortion care where it’s less restricted. Even if she isn’t able to provide abortions at all, she says that there are still ways to help patients get safe, above-board abortions so as not to repeat the dangerous and often gruesome outcomes of self-induced abortions or those done by illegitimate practitioners before Roe.

“One of the roles that I think I can have as a physician is helping people with wraparound care for self-managed abortion,” says Robin. “If they can get the [abortion] pills online, then I can do the ultrasound beforehand, I can do the ultrasound after, I can talk them through it. I can help them with all the aspects of this care, I just can’t give them the pills myself.”

Whether a doctor can be penalized for “aiding and abetting” abortions that happen in different states remains an open question. In Texas, for example, Senate Bill 8 – which took effect Sept. 1, 2021 – not only established a fetal heartbeat law but added language that would allow private citizens to sue anyone who “knowingly engages in conduct that aids or abets the performance or inducement of an abortion” or anyone who even intends to do so.

That’s what happened to Alan Braid, MD, an ob.gyn. based in San Antonio. He confessed in a Washington Post op-ed that he had performed an abortion after cardiac activity had been detected in the pregnancy. Aware of the legal risks, he has since been sued by three people, and those cases are still underway.

But Ms. Ziegler says the chances of a doctor from a progressive state actually getting extradited and prosecuted by a state with restrictive abortion laws is pretty low – not zero, but low.

Like Robin, Natalie – an ob.gyn. in her early 30s – is a complex family planning fellow in Massachusetts. After her fellowship, she wants to return to Texas, where she completed her residency training.

“I’m at the point in my training where everyone starts looking for jobs and figuring out their next steps,” says Natalie. “The Dobbs decision introduced a ton of chaos due to the vagueness in the laws and how they get enforced, and then there’s chaos within institutions themselves and what kind of risk tolerance they have.”

Looking towards her future career path, Natalie says that she would not consider a job at an institution that didn’t allow her to teach abortion care to students, speak publicly about abortion rights, or let her travel outside of Texas to continue providing abortion care. She’s also preemptively seeking legal counsel and general guidance – advice that Ms. Ziegler strongly urges doctors to heed, sooner rather than later.

In states that have strict abortion bans with exceptions for life-threatening cases, there is still a lack of clarity around what is actually considered life-threatening enough to pass as an exception.

“Is it life-threatening in the next 6 hours? 24 hours? Seven days? One month?” Robin asks. “In medicine, we don’t necessarily talk about if something is life-threatening or not, we just say that there’s a high risk of X thing happening in X period of time. What’s the threshold at which that meets legal criteria? Nobody has an answer for that.”

Robin explains that, in her patients who have cancer, a pregnancy wouldn’t “necessarily kill them within the span of the next 9 months, but it could certainly accelerate their disease that could kill them within the next year or two.”

Right now, she says she doesn’t know what she would do if and when she is put in that position as a doctor.

“I didn’t go to medical school and become a doctor to become a felon,” says Robin. “Our goal is to make as many legal changes as we can to protect our patients and then practice as much harm reduction and as much care as we can within the letter of the law.”

A version of this article first appeared on WebMD.com.

The Canadian Task Force on Preventive Health Care recommends against the routine screening of all pregnant and postpartum women for depression using a standard questionnaire, according to its new guideline.

The basis for its position is the lack of evidence that such screening “adds value beyond discussions about overall wellbeing, depression, anxiety, and mood that are currently a part of established perinatal clinical care.

“We should not be using a one-size-fits all approach,” lead author Eddy Lang, MD, professor and head of emergency medicine at the Cumming School of Medicine, University of Calgary (Alta.), told this news organization.

Instead, the task force emphasizes regular clinical care, including asking patients about their wellbeing and support systems. The task force categorizes the recommendation as conditional and as having very low-certainty evidence.

The recommendation was published in CMAJ.
 

One randomized study

The task force is an independent panel of clinicians and scientists that makes recommendations on primary and secondary prevention in primary care. A working group of five members of the task force developed this recommendation with scientific support from Public Health Agency of Canada staff.

In its research, the task force found only one study that showed a benefit of routine depression screening in this population. This study was a randomized controlled trial conducted in Hong Kong. Researchers evaluated 462 postpartum women who were randomly assigned to receive screening with the Edinburgh Postnatal Depression Scale (EPDS) or no screening 2 months post partum.

“We found the effect of screening in this study to be very uncertain for the important outcomes of interest,” said Dr. Lang.

“These included parent-child stress, marital stress, and the number of infant hospital admissions. The effects of screening on all of these outcomes were very uncertain, mainly because it was such a small trial,” he said.

The task force also assessed how pregnant and postpartum women feel about being screened. What these women most wanted was a good relationship with a trusted primary care provider who would initiate discussions about their mental health in a caring atmosphere.

“Although they told us they liked the idea of universal screening, they admitted to their family doctors that they actually preferred to be asked about their wellbeing, [to be asked] how things were going at home, and [to have] a discussion about their mental health and wellbeing, rather than a formal screening process. They felt a discussion about depression with a primary health care provider during the pregnancy and postpartum period is critical,” said Dr. Lang.

Thus, the task force recommends “against instrument-based depression screening using a questionnaire with cutoff score to distinguish ‘screen positive’ and ‘screen negative’ administered to all individuals during pregnancy and the postpartum period (up to 1 year after childbirth).”
 

Screening remains common

“There’s a lot of uncertainty in the scientific community about whether it’s a good idea to administer a screening test to all pregnant and postpartum women to determine in a systematic way if they might be suffering from depression,” said Dr. Lang.

The task force recommended against screening for depression among perinatal or postpartum women in 2013, but screening is still performed in many provinces, said Dr. Lang.

Dr. Lang emphasized that the recommendation does not apply to usual care, in which the provider asks questions about and discusses a patient’s mental health and proceeds on the basis of their clinical judgment; nor does it apply to diagnostic pathways in which the clinician suspects that the individual may have depression and tests her accordingly.

“What we are saying in our recommendation is that all clinicians should ask about a patient’s wellbeing, about their mood, their anxiety, and these questions are an important part of the clinical assessment of pregnant and postpartum women. But we’re also saying the usefulness of doing so with a questionnaire and using a cutoff score on the questionnaire to decide who needs further assessment or possibly treatment is unproven by the research,” Dr. Lang said.
 

A growing problem

For Diane Francoeur, MD, CEO of the Society of Obstetricians and Gynecologists of Canada, this is all well and good, but the reality is that such screening is better than nothing.

Quebec is the only Canadian province that conducts universal screening for all pregnant and postpartum women, Dr. Francoeur said in an interview. She was not part of the task force.

“I agree that it should be more than one approach, but the problem is that there is such a shortage of resources. There are many issues that can arise when you follow a woman during her pregnancy,” she said.

Dr. Francoeur said that COVID-19 has been particularly tough on women, including pregnant and postpartum women, who are the most vulnerable.

“Especially during the COVID era, it was astonishing how women were not doing well. Their stress level was so high. We need to have a specific approach dedicated to prenatal mental health, because it’s a problem that is bigger than it used to be,” she said.

Violence against women has increased considerably since the beginning of the COVID-19 pandemic, said Dr. Francoeur. “Many more women have been killed by their partners. We have never seen anything like this before, and I hope we will never see this again,” she said.

“Help was more available a few years ago, but now, it’s really hard if and when you need to have a quick consultation with a specialist and the woman is really depressed. It can take forever. So, it’s okay to screen, but then, what’s next? Who is going to be there to take these women and help them? And we don’t have the answer,” Dr. Francoeur said.

Pregnant and postpartum women who suffer from depression need more than pills, she added. “We reassure them and treat their depression pharmacologically, but it’s also a time to give appropriate support and help them through the pregnancy and get well prepared to receive their newborn, because, as we now know, that first year of life is really important for the child, and the mom needs to be supported.”

Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada. Dr. Lang and Dr. Francoeur reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Canadian Task Force on Preventive Health Care recommends against the routine screening of all pregnant and postpartum women for depression using a standard questionnaire, according to its new guideline.

The basis for its position is the lack of evidence that such screening “adds value beyond discussions about overall wellbeing, depression, anxiety, and mood that are currently a part of established perinatal clinical care.

“We should not be using a one-size-fits all approach,” lead author Eddy Lang, MD, professor and head of emergency medicine at the Cumming School of Medicine, University of Calgary (Alta.), told this news organization.

Instead, the task force emphasizes regular clinical care, including asking patients about their wellbeing and support systems. The task force categorizes the recommendation as conditional and as having very low-certainty evidence.

The recommendation was published in CMAJ.
 

One randomized study

The task force is an independent panel of clinicians and scientists that makes recommendations on primary and secondary prevention in primary care. A working group of five members of the task force developed this recommendation with scientific support from Public Health Agency of Canada staff.

In its research, the task force found only one study that showed a benefit of routine depression screening in this population. This study was a randomized controlled trial conducted in Hong Kong. Researchers evaluated 462 postpartum women who were randomly assigned to receive screening with the Edinburgh Postnatal Depression Scale (EPDS) or no screening 2 months post partum.

“We found the effect of screening in this study to be very uncertain for the important outcomes of interest,” said Dr. Lang.

“These included parent-child stress, marital stress, and the number of infant hospital admissions. The effects of screening on all of these outcomes were very uncertain, mainly because it was such a small trial,” he said.

The task force also assessed how pregnant and postpartum women feel about being screened. What these women most wanted was a good relationship with a trusted primary care provider who would initiate discussions about their mental health in a caring atmosphere.

“Although they told us they liked the idea of universal screening, they admitted to their family doctors that they actually preferred to be asked about their wellbeing, [to be asked] how things were going at home, and [to have] a discussion about their mental health and wellbeing, rather than a formal screening process. They felt a discussion about depression with a primary health care provider during the pregnancy and postpartum period is critical,” said Dr. Lang.

Thus, the task force recommends “against instrument-based depression screening using a questionnaire with cutoff score to distinguish ‘screen positive’ and ‘screen negative’ administered to all individuals during pregnancy and the postpartum period (up to 1 year after childbirth).”
 

Screening remains common

“There’s a lot of uncertainty in the scientific community about whether it’s a good idea to administer a screening test to all pregnant and postpartum women to determine in a systematic way if they might be suffering from depression,” said Dr. Lang.

The task force recommended against screening for depression among perinatal or postpartum women in 2013, but screening is still performed in many provinces, said Dr. Lang.

Dr. Lang emphasized that the recommendation does not apply to usual care, in which the provider asks questions about and discusses a patient’s mental health and proceeds on the basis of their clinical judgment; nor does it apply to diagnostic pathways in which the clinician suspects that the individual may have depression and tests her accordingly.

“What we are saying in our recommendation is that all clinicians should ask about a patient’s wellbeing, about their mood, their anxiety, and these questions are an important part of the clinical assessment of pregnant and postpartum women. But we’re also saying the usefulness of doing so with a questionnaire and using a cutoff score on the questionnaire to decide who needs further assessment or possibly treatment is unproven by the research,” Dr. Lang said.
 

A growing problem

For Diane Francoeur, MD, CEO of the Society of Obstetricians and Gynecologists of Canada, this is all well and good, but the reality is that such screening is better than nothing.

Quebec is the only Canadian province that conducts universal screening for all pregnant and postpartum women, Dr. Francoeur said in an interview. She was not part of the task force.

“I agree that it should be more than one approach, but the problem is that there is such a shortage of resources. There are many issues that can arise when you follow a woman during her pregnancy,” she said.

Dr. Francoeur said that COVID-19 has been particularly tough on women, including pregnant and postpartum women, who are the most vulnerable.

“Especially during the COVID era, it was astonishing how women were not doing well. Their stress level was so high. We need to have a specific approach dedicated to prenatal mental health, because it’s a problem that is bigger than it used to be,” she said.

Violence against women has increased considerably since the beginning of the COVID-19 pandemic, said Dr. Francoeur. “Many more women have been killed by their partners. We have never seen anything like this before, and I hope we will never see this again,” she said.

“Help was more available a few years ago, but now, it’s really hard if and when you need to have a quick consultation with a specialist and the woman is really depressed. It can take forever. So, it’s okay to screen, but then, what’s next? Who is going to be there to take these women and help them? And we don’t have the answer,” Dr. Francoeur said.

Pregnant and postpartum women who suffer from depression need more than pills, she added. “We reassure them and treat their depression pharmacologically, but it’s also a time to give appropriate support and help them through the pregnancy and get well prepared to receive their newborn, because, as we now know, that first year of life is really important for the child, and the mom needs to be supported.”

Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada. Dr. Lang and Dr. Francoeur reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Canadian Task Force on Preventive Health Care recommends against the routine screening of all pregnant and postpartum women for depression using a standard questionnaire, according to its new guideline.

The basis for its position is the lack of evidence that such screening “adds value beyond discussions about overall wellbeing, depression, anxiety, and mood that are currently a part of established perinatal clinical care.

“We should not be using a one-size-fits all approach,” lead author Eddy Lang, MD, professor and head of emergency medicine at the Cumming School of Medicine, University of Calgary (Alta.), told this news organization.

Instead, the task force emphasizes regular clinical care, including asking patients about their wellbeing and support systems. The task force categorizes the recommendation as conditional and as having very low-certainty evidence.

The recommendation was published in CMAJ.
 

One randomized study

The task force is an independent panel of clinicians and scientists that makes recommendations on primary and secondary prevention in primary care. A working group of five members of the task force developed this recommendation with scientific support from Public Health Agency of Canada staff.

In its research, the task force found only one study that showed a benefit of routine depression screening in this population. This study was a randomized controlled trial conducted in Hong Kong. Researchers evaluated 462 postpartum women who were randomly assigned to receive screening with the Edinburgh Postnatal Depression Scale (EPDS) or no screening 2 months post partum.

“We found the effect of screening in this study to be very uncertain for the important outcomes of interest,” said Dr. Lang.

“These included parent-child stress, marital stress, and the number of infant hospital admissions. The effects of screening on all of these outcomes were very uncertain, mainly because it was such a small trial,” he said.

The task force also assessed how pregnant and postpartum women feel about being screened. What these women most wanted was a good relationship with a trusted primary care provider who would initiate discussions about their mental health in a caring atmosphere.

“Although they told us they liked the idea of universal screening, they admitted to their family doctors that they actually preferred to be asked about their wellbeing, [to be asked] how things were going at home, and [to have] a discussion about their mental health and wellbeing, rather than a formal screening process. They felt a discussion about depression with a primary health care provider during the pregnancy and postpartum period is critical,” said Dr. Lang.

Thus, the task force recommends “against instrument-based depression screening using a questionnaire with cutoff score to distinguish ‘screen positive’ and ‘screen negative’ administered to all individuals during pregnancy and the postpartum period (up to 1 year after childbirth).”
 

Screening remains common

“There’s a lot of uncertainty in the scientific community about whether it’s a good idea to administer a screening test to all pregnant and postpartum women to determine in a systematic way if they might be suffering from depression,” said Dr. Lang.

The task force recommended against screening for depression among perinatal or postpartum women in 2013, but screening is still performed in many provinces, said Dr. Lang.

Dr. Lang emphasized that the recommendation does not apply to usual care, in which the provider asks questions about and discusses a patient’s mental health and proceeds on the basis of their clinical judgment; nor does it apply to diagnostic pathways in which the clinician suspects that the individual may have depression and tests her accordingly.

“What we are saying in our recommendation is that all clinicians should ask about a patient’s wellbeing, about their mood, their anxiety, and these questions are an important part of the clinical assessment of pregnant and postpartum women. But we’re also saying the usefulness of doing so with a questionnaire and using a cutoff score on the questionnaire to decide who needs further assessment or possibly treatment is unproven by the research,” Dr. Lang said.
 

A growing problem

For Diane Francoeur, MD, CEO of the Society of Obstetricians and Gynecologists of Canada, this is all well and good, but the reality is that such screening is better than nothing.

Quebec is the only Canadian province that conducts universal screening for all pregnant and postpartum women, Dr. Francoeur said in an interview. She was not part of the task force.

“I agree that it should be more than one approach, but the problem is that there is such a shortage of resources. There are many issues that can arise when you follow a woman during her pregnancy,” she said.

Dr. Francoeur said that COVID-19 has been particularly tough on women, including pregnant and postpartum women, who are the most vulnerable.

“Especially during the COVID era, it was astonishing how women were not doing well. Their stress level was so high. We need to have a specific approach dedicated to prenatal mental health, because it’s a problem that is bigger than it used to be,” she said.

Violence against women has increased considerably since the beginning of the COVID-19 pandemic, said Dr. Francoeur. “Many more women have been killed by their partners. We have never seen anything like this before, and I hope we will never see this again,” she said.

“Help was more available a few years ago, but now, it’s really hard if and when you need to have a quick consultation with a specialist and the woman is really depressed. It can take forever. So, it’s okay to screen, but then, what’s next? Who is going to be there to take these women and help them? And we don’t have the answer,” Dr. Francoeur said.

Pregnant and postpartum women who suffer from depression need more than pills, she added. “We reassure them and treat their depression pharmacologically, but it’s also a time to give appropriate support and help them through the pregnancy and get well prepared to receive their newborn, because, as we now know, that first year of life is really important for the child, and the mom needs to be supported.”

Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada. Dr. Lang and Dr. Francoeur reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.